Drug-nutrient interactions in renal failure

Clinical

Briefs

Drug-Nutrient Renal Failure

Interactions

Nancy A. Mason, PharmD,*

and Sharon M. Boyd, MS, RDt

D

IETITIANS have always played an important role in the treatment of patients with renal failure. The general emphasis of this role has been patient education regarding dietary restrictions with the goals of preventing the progression of renal failure and minimizing the complications of hyperkalemia, hyperphosphatemia, and hypoalbuminemia as renal failure progresses to end stage. In the renal transplant patient, nutrition education is centered on the prevention of hypercholesterolemia and hyperglycemia related to immunosuppressive medications. An expanded role for dietitians and pharmacists recently has been set forth by the Joint Commission on Accreditation of Healthcare Organizations (JCAHO), which requires that patients be provided with instruction on potential drug-food interactions.’ Thus, these health professionals must work together to assume the roles of monitoring the potential for these interactions in hospitalized patients as well as counseling patients about avoidance of drug-nutrient interactions as they manage therapy at home. Although this JCAHO guideline has beneficial implications for all patients, the potential benefit of monitoring drug-nutrient interactions is especially significant for patients with chronic renal failure. These patients *Cbrwa/Asastant Professor, The Unwersity of M/ch/gan College of Pharmacy and Clinical Pharmacist in Nephrology at Unwersity Hospitals, Ann Arbor, MI. fRenal Dietitian, llnwersity Hospitals, Ann Arbor, MI. Address reprint requests to Nancy A. Mason, PharmD, The University of Michigan College of Pharmacy, 428 Church St, Ann Arbor, Ml 481091065. o 1995 by the Nabonal Kidney Foundatjon, Inc. 1051-2276/95/0504-006$03.00/O

214

Journal

of Renal

in

are susceptible to clinically significant drugnutrient interactions for many reasons, not the least of which is the sheer number of medications prescribed. A recent characterization of patients on hemodialysis found that on average each patient took 12 medications* Although there have been no studies specifically targeting drug-nutrient interactions in patients with renal failure, the potential for reduced absorption of calcium and iron salts when given with food or antacids was identified as a potential problem in several patients in this study.* The purpose of this review is to provide the renal dietitian with practical guidelines for addressing and accomplishing the demands of this new role. Specifically, this article reviews the effect of renal failure on the absorption of drugs and nutrients and the mechanisms by which clinically significant drug-nutrient interactions occur. Tables are provided to allow quick assess to information about the medications most commonly used by this patient population, and an approach for data collection and assessment of the potential for drug-nutrient interactions is proposed.

SIGNIFICANCE DRUG-NUTRIENT

OF INTERACTIONS

The topic of drug-nutrient interactions has not been well studied. Very little is known about the significance of these interactions in causing adverse drug reactions or impaired nutritional status. Generally, this issue only becomes important to healthcare providers and patients after a serious adverse event has occurred. For this reason, it is important to be aware of comNutrition,

Vol5,

No 4 (October),

1995:

pp 214-222

DRUG-NUTRIENT

INTERACTIONS

IN RENAL

215

FAILURE

monly occurring interactions and to monitor patients to avoid potential adverse effects. Adverse drug reactions that result from drug-nutrient interactions include those outcomes that lead to subtherapeutic effects as well as drug toxicity. The most common type of drug-nutrient interaction involves loss of therapeutic effect when a food substance slows or impairs drug absorption Less commonly, a food substance may stimulate drug metabolism or block the effect of the drug through other mechanisms. The most important clinical outcomes related to changes in nutritional status generally result from long-term use of drugs that cause changes In the absorption, catabolism, or elimination of nutrients 3a4 Drug-nutrient interactions can result in positive or negative outcomes related to disease state control. For example, aluminum- or calcium-containing antacids bind dietary phosphate in the gastrointestinal tract in a positive therapeutrc way to benefit patients with chronic renal failure by reducing serum phosphate concentrations. Conversely, binding of phenytoin by the components contained in tube feeding formulations could result in loss of seizure control and a negative clinrcal outcome. Not all drug-nutrient interactions have clinically significant consequences. Whether a change in drug absorption related to a drug-nutrient interaction is clinically significant depends on the extent of the interaction and the therapeutic concentration range of the drug. A drug with a broad therapeutic concentration range is less likely to exhibit a clrnically apparent change in therapeutic effect than a drug with a very narrow therapeutic range when a small alteration in absorption is encountered.5 Thus, a change in the absorption of a drug like digoxin, which has a very narrow therapeutic range, would have a high potential for clinically significant consequences. The presence of a drug-nutrient interaction does not necessarily mean that the drug cannot be taken with food or with the interacting nutrient. However, knowledge of the potential interaction and careful monitoring and adjustment of drug dosage regi-

mens may be warranted to avoid adverse events resulting from an interaction.

EFFECT OF RENAL THE ABSORPTION AND NUTRIENTS

FAILURE ON OF DRUGS

It is well known that renal failure can have significant effects on the distribution, metabolism, and elimination of many medications. These changes, along with an increased sensitivity of the uremic patient to the effects of some medications and the administration of multiple concurrent medications, contribute to the potential for adverse events for patients with renal failure.6,7 Similarly, patients with renal failure are often prone to poor nutritional status, with protein-calorie malnutrition contributing to the morbidity and mortality of this disease.*-i0 However, very little is known about the physiological effects of renal failure on the absorption (bioavailability) of drugs and nutrients. Theoretically, renal failure can impair gastrointestinal absorption through several mechanisms, including reduced motility of the gastrointestinal tract, increased gastric pH, edema of the gastrointestinal tract, and antacid treatment. Also, common gastrointestinal uremic symptoms, such as poor appetite, nausea, vomiting, and diarrhea, could contribute to poor dietary nutrient intake and utilization as well as reduced drug absorption.6z11 After a drug is absorbed into the bloodstream, first-pass metabolism by the liver can also influence the amount of an agent that ultimately reaches the systemic circulation. Impaired metabolism leading to increased bioavailability in patients with renal failure has been shown for several medicatrons, but this has been shown to be clrnrcally significant in very few cases 6 Although all of these physiological factors point to the probability of changes in drug bioavailability, there are very few clinical studies in this area. The potential for accentuation of these potential changes in drug absorption by drug-nutrient Interactions underscores the need for diligent monitoring of this patient population.

216

MASON

MECHANISMS DRUG-NUTRIENT

INVOLVED IN INTERACTIONS

The most common mechanisms causing drug-nutrient interactions in patients with renal failure involve reductions in the absorption of the drug or nutritional component. Other mechanisms involving changes in metabolism, excretion, and influence on drug effect at the site of action are less common. Therefore, the discussion below is centered on the mechanisms related primarily to absorption of the drug or nutrient.

Drug Concentration

Alteration

Several steps are involved in the process of drug absorption by the oral route of administration. Before the drug can be absorbed, it must first disintegrate and be dissolved in the gastric contents. Many factors can affect the degree of dissolution in the stomach and may contribute to altered absorption of the medication, including food in the stomach and changes in gastric pH. Food tends to delay stomach emptying, thus leading to greater drug dissolution, the possibility of delayed or diminished drug action, and increased potential for drug-nutrient interactions. Changes in gastric pH may cause enhancement of these interactions and contribute to interactions involving chelation of drugs with nutrient molecules to form insoluble complexes. Food also may increase splanchnic blood flow, which may influence the absorption of drugs that are extensively metabolized during the first pass through the liver.5,12,13,14

Nutrient

Status Alteration

Drugs can interact to cause reduced absorption of nutrients in several ways. The most direct interaction is chelation or complexation of the drug entity with a nutrient in the GI tract to prevent absorption. Another important mechanism by which drugs may reduce nutrient absorption is by altering the integrity of the GI tract, causing mucosal damage at the site of absorption of a specific nutrient. Drugs also may interact to cause changes in nutrient availability

AND

BOYD

through indirect mechanisms, such as depletion of a nutrient essential to the action of a secondary nutrient (eg, vitamin D being required for calcium absorption) or by causing changes in electrolyte concentrations through their pharmacological actions, which may cause retention or depletion of various electrolytes or nutrients.73,14 Mechanisms involving stimulation or suppression of appetite and changes in glycemic or cholesterolemic control caused by the action of a drug also may contribute to alterations in nutrient status.3,14

Antacids Antacids deserve special consideration in this discussion of drug-nutrient interactions. Aluminumand calcium-containing antacid salts are used extensively in patients with chronic renal failure for their therapeutic phosphate-binding effecti These agents can also interact with other drugs and nutrients through antacid-induced increases in gastric pH and by chelating with these agents. Antacids have been shown to delay or decrease the absorption of many drugs and nutrients because of these mechanisms.i6~i7 Potential drug-antacid interactions in patients with renal failure are shown in Table 1. This table was prepared specifically for renal failure patients; thus, only drugs interacting with aluminumor calcium-containing antacids were included. This table should be used as a guide only because research in the area of antacid-drug interactions and antacidnutrient interactions is incomplete. Absence of a drug does not necessarily mean that it does not interact with antacids; it may have not been studied. It is recommended that antacids be administered at least 2 hours before or after administration of an interacting drug.14

Tube

Feedings

The use of enteral feeding formulas can create particular problems with drug interactions because of the general practice of administering drugs through the feeding tube while the nutrient solution is infusing.

DRUG-NUTRIENT

INTERACTIONS

TABLE 1. Significant AluminumUsed in Renal Failure,

IN

RENAL

or Calcium-Containing Antacid Dialysis, and Transplantation

Unknown Alkaline pH reduces Adsorptron

supplements

H2 receptor antagonists Crmetidine Ranitidine Iron supplements Phenytoin Prednisone Propranolol Quinolones Ciprofloxacin Norfloxacrn Ofloxacin Sodium polystyrene sulfonate Sucralfate

from

Murray

With

and

Healy,13

Drugs

Commonly

Recommendation/ Comment Separate Separate Monitor doses

absorptron

doses by 2 1 h doses digoxin effect, separate to avoid potential Interactron

Adsorption

Separate

doses

by 2 2 h

Chelation or Increased pH None Adsorption Delay In gastric emptying Chelatron

Separate

doses

by 2 2 h

Antacids

brnd

resin

Instead

Potential loss of efficacy Increased gastric pH None

Warfarin Data

Interactions

Mechanism

Drug/Nutrient Drugs Atenolol Calcrum Drgoxrn

217

FAILURE

Prnson

and

Weart,r6

The interaction of drugs with tube feeding formulas can result in reduced drug and nutrient absorption. Of particular significance is the interaction of phenytoin suspension with enteral formulas, which results in reduced phenytoin bioavailability and potential loss of seizure control.‘* One recommendation for dealing with this issue is to hold the enteral feeding for 2 hours before and after phenytoin suspension administration and to flush the feeding tube with 60 mL of water after the dose is administered.18 However, others have found that this technique does little to improve the bioavailability of phenytoin.lg There is some evidence that phenytoin capsules may interact less frequently with enteral formulas than the suspension, although further study is needed before a general recommendation to change to the capsule formulation is warranted.‘O Most agree that the emphasis should be placed on monitoring phenytoln serum concentrations and increasing the dose of phenytoin to compensate for any reduction in absorption because of the tube feedings. Conversely, if the enteral feedings

and

Clinical significance Clinical significance Separate doses

of HC03 because

D’Arcy

of

and

Metabolrc byr2h Separate

McElnay

alkalosrs; doses

(3) (3) by 2 3 h

separate

doses

by 2 30 mm

I7

are discontinued, phenytoin dosage may need to be reduced.lg Physical incompatibilities between the drug and the tube feeding formulas also may cause interactions in the form of gelling or precipitation leading to possible blockage of the feeding tube.4 Some liquid drug formulations that may be physically Incompatible with enteral formulas, among others reported by one group of investigators,21 include ferrous sulfate elixir, phenytoin suspension, and digoxin elixir. To avoid these interactions, Gora Tschampel, and Visconti2* proposed some basic principles for administering drugs to patients receiving enteral nutrition. These include giving the drugs by mouth if possible, using liquid rather than solid dosage forms, flushing the feeding tube with at least 30 mL of water before and after medication administration, diluting highly concentrated solutions with at least 60 mL of water, separating drugs administered at the same time by flushing with 5 mL of water between each one, and avoiding direct administration of medications Into the enteral formula.

218

MASON

TABLE 2. Commonly

Used Medications

Generic

Name

Analgesics Narcotics Codeine Hydromorphone Levorphanol Oxycodone Methadone Morphrne NSAIDS Ibuprofen lndomethacin Piroxicam Sullndac Others Acetaminophen Aspirin

Propoxyphene AntlcoagulanUantiplatelet agents Aspirin (see above) Warfann

Antidiabetic Glipizide Glyburide Anticonvulsants Phenytoin

BOYD

in Renal Failure, Dialysis, and Transplantation Timing

of Administration

NutntlonalfDrug

Take

with

food

to minimize

GI distress

Anorexia,

Take

with

food

to mlnlmlze

Gl distress

Nausea, vomiting, abdominal pain

Take without Take with food take with a reduce risk Take without

regard to food to minimize GI distress, full glass of water to of lodging In esophagus regard to food

constipation,

lleus

dyspepsia,

GI intolerance, bleeding, delay absorption Food

increases

Risk

food

may

absorption

Best to avoid taking with meals; administration time should be consistent from day to day

Consistent intake of vitamin K essential; high Intake reduces effectiveness, whereas low intake increases effectiveness; use of enteral formuias with vitamin K may reduce effectiveness; hypoalbuminemia may cause increased sensitivity to warfarin

Take

before

Food

Take

with

food

to minimize

GI distress

Take

with

food

to minimize

GI distress

Take

without

agents

Carbamazeplne AntihistamInes Dtphenhydramine Hydroxyzlne Antihypertensives ACE inhibitors Benazepril Captopril Enalapril Fosinopril Lisinopnl Ramlpnl Beta blockers Atenolol Metoprolol Propranolol

AND

Take without captopril,

Take

without

Take Take

with with

breakfast

regard

absorption

Enteral formulas decrease bloavailab&y, monitor drug concentrations; hypoalbuminemia may cause increased sensitivity to phenytoln, food increases absorption; vitamin B12, vitamin D, or folate supplementation may be needed Dry mouth, nausea, vomiting, diarrhea, food increases absorption

to food

regard to food take 1 h before

regard

delays

(except meals)

Food reduces absorption of captopril; avoid salt substitutes; use caution with potassium supplementation; ACE inhibitors Increase serum potassium

to food

Separate antacids by 1 h, food delay absorption Food increases absorption Food increases absorption

food food (Contmued

on next

page)

may

DRUG-NUTRIENT INTERACTIONS IN RENAL FAILURE TABLE 2. Commonly

Used Medications

Generic

Name

Alpha/beta blocker Labetolol Calcrum channel blockers Amlodipine Diltiazem lsradrpine Nifedrprne Verapamil

Centrally acting adrenergic agents Clonidine Methyldopa Peripherally acting antiad renergic agents Doxazosin Prazosin Terazosrn Vasodrlators Hydralazrne Minoxidil Anti-rnfectnes Antifungal/antiviral Acyclovrr Fluconazole Flucytosrne Ketoconazole Nystatrn Cephalosporins Cefaclor Cefixime Cefuroxime Cephalexin Cephradine Penicillins Amoxrcrllrn AmoxicillirUclavulanate Ampicillrn Quinolones Ciprofloxacin Norfloxacin Ofloxacin Tetracylrnes Tetracyclrne

219

in Renal Failure, Dialysis, and Transplantation Timing

Take

with

Take Take Take Take

without 1 hour without wrthout

Nutritional/Drug

of Admrnistratron

food

Food

regard before regard regard

to food meals to food to food

Take SR with forms may to food

food; other dosage be taken without regard

Take

without

regard

to food

Take

without

regard

to food

Take Take

with food wtthout regard

to food

Take Take Take Take

with food to minimize GI distress without regard to food without regard to food with food to mrnrmrze GI distress

Take

without

regard

to food

Take

wrthout

regard

to food

Take wrth Take with Take wrth meal Take

without

regard

Take with a full glass before or 2 h after Take without regard

GI distress GI distress or 2 h after

to food of water meal to food

1 h

Demeclocycline Doxycyclrne

Take

food

to minimize (Contmued

Increases

Rusk

absorptron

a low-fat

meal

absorption

Nausea,

vomrtrng,

diarrhea

Nausea, by22h

vomiting;

separate

antacrds

Diarrhea

Take with a full glass of water 1 h before or 2 h after meal Take 1 h before or 2 h after meal with

increases

AdmInistratIon wtth prevent flushing Constipation

Food

food to mrnrmrze food to minimize water, 1 h before

(Cont’d)

GI distress on next

page)

Food Diarrhea;

reduces food

absorption reduces

Separate ments Separate ments Separate ments

antacids by r3 h antacids by 23 h antacids by 23 h

Separate ments Separate ments Separate ments

antacids by 23 h antacids by 23 h antacids by r3 h

absorption

& mrneral

supple-

& mineral

supple-

& mineral

supple-

& mineral

supple-

& mrneral

supple-

& mineral

supple-

may

220

MASON

TABLE 2. Commonly

Used

Generic

Medications

in Renal

Name

Macrolides Azithromycin Clarithromycin Erythromycin

Others Clrndamycin Metronrdazole Rifampin

Trimethoprimlsulfamethoxazole Vancomycrn Cardiac agents Digoxrn

Failure,

Timtng

Food

Take wrth food or a full glass of water to minimize esophageal irritation Take with food to minimize GI distress Take with a full glass of water 1 h before or 2 h after a meal; may take with food to minimize GI drstress Take with food and a full glass of water

Pseudomembranous

Take

without

regard

Avoid taking with pectin meal

Risk

absorptron

Epigastric distress, abdominal food reduces absorption

Food Food

pain,

colitis

may delay absorption reduces absorption

to food high-fiber

Take

with

food

Take

with

food

Take

without

Take

1 I2 h before

Sucralfate

Take

1 h before

meals

Omeprazole Sterords Methylprednrsolone Prednrsone

Take

just

before

meals

Take

with

food

to minimize

Take

1 h before

Thyroid Levothyroxine Thyroid lmmunosuppressives Azathioprine Cyclosporine

reduces

BOYD

(Cont’d)

Nutntronal/Drug

Take 1 h before or 2 h after meal Take without regard to meals Take 1 h before or 2 h after meal, may take with food to minimize GI distress

1 h before

Thiazides Chlorothiazide Chlorthalidone Hydrochlorothrazrde Metolazone Gastrointestinal agents HP receptor blockers Cimetidine Famotrdrne Nrzattdine Ranitidrne Others Metoclopramide

and Transplantation

of Administration

Take

Nitrates Diuretics Loop diuretics Bumetanide Furosemide

Dialysis,

AND

or hrgh-

or 2 h after

to minimize

Separate doses from antacids: hypoalbumrnemia may increase risk of toxicity; food may delay absorption

meal

GI distress

Potassium depleting: may blood glucose & reduce food may delay absorption semide

increase calcium; of furo-

Potassium depleting; may increase blood glucose & reduce calcium, food increases absorption of chlorothiazide and hydrochlorothazrde

regard

to food

Separate antacids or iron supplements by 2 2 h, food may delay absorptron of crmetrdrne

Nausea, diarrhea; incompatible with some enteral formulas Separate antacids by 2 30 min; caution re: aluminum content in ESRD Separate iron supplements by 2 2 h

meals

or 2 h after

GI distress

Increased appetite with weight gain, fluid retention, calcrum wastrng, protern catabolism, Increased glucose levels

meals

Food

Take with food to mrnrmrze GI distress Mix with milk, chocolate milk, or orange juice at room temperature in glass container (Contmed

on next

page)

decreases

Increased levels

potassium

absorption

& cholesterol

DRUG-NUTRIENT

TABLE 2. Commonly Generic Phosphate Aluminum

INTERACTIONS

Used

Medications

Name

calcium

Vrtamrns and minerals Calcitriol Fokc acid Ferrous sulfate

Renal

RENAL

in Renal Timing

binders antacids

Calcium acetate, carbonate

IN

Failure,

Dialysis,

FIGURE Example line: Put mealtimes. taken at

Separate Iron constipation Separate iron constrpation

phosto

GI

Risk

supplements

by 2 2 h,

supplements

by 2 2 h;

Increased calcium absorption Separate zinc supplement by 2 2 h Nausea, vomiting, dyspepsia; food decreases absorption, separate antacids by r2 h

meals drugs;

ACE, angiotensin-convertrng and Welling,5 Welling,12 Pinson and American Society of Hospital

enzyme, and Weart,‘6 Pharmacrstsz5

D’Arcy

less well-recognized but equally important goal is to promote positive interactions that benefit the patient’s clinical status. For example, in the patient with chronic renal failure, calcium salts are often prescribed with the goal of binding dietary phosphate and therefore would need to be administered with meals for optimal effectiveness. However, in some cases calcium salts are prescribed as nutritional supplements to boost serum calcium levels, in which case administration between meals would maximize drug absorption. In the case of iron supplementation, administration between meals is best for iron absorption. Patient intolerance in the form of gastrointestinal distress often precludes this goal, however, and leads us to compromise drug absorption and recommend iron administration with meals to maintain patient compliance. Collaboration between the dietitian and pharmacist is essential in defining the clinical plan for monitoring and assessment of drug-nutrient interactions. Pharmacists can provide specific drug information as well as

Standard nutritional assessment of patients with chronic renal failure includes such monitoring parameters as weight; protein status; serum electrolyte, calcium, phosphate, magnesium, glucose, and cholesterol levels; fluid status; and blood pressure. To assess the potential for drug-nutrient interactions, information concerning medications and their regimens (Table 2), specific timing of medication administration, and times of meals also must be obtarned from the patlent. One way for this information to be easily assessed is through the use of a time line as a visual aid to correlate food intake with drug Intake (Fig 1). The time line may also serve as a useful educational tool to help patients plan their drug dosing times to optimize administration with regard to meals. The obvious goal of this monitoring and assessment approach is to avoid or minimize negative drug-nutrient interactions. A morninu afternoon 8 9 10 11 12 1 2 3 4 noon

phos-

meals meals after meals; to mrnrmrze

CLINICAL MONITORING AND ASSESSMENT OF POTENTIAL DRUG-NUTRIENT INTERACTIONS

7

(Cont’d)

Nutntronal/Drug

Take with food to bind dietary phate Take with food to bind dietary phate, take between meals increase calcium absorption

Abbreviations: NSAIDs, nonsteroidal anti-inflammatory Data from Williams, Davis, and Lowenthal,3 Roe,4Toothaker and McElnay,” Drug Facts and Comparisonsz3 Pronsky,*4

6 am

and Transplantation

of Admrnrstratron

Take without regard to Take without regard to Take 1 h before or 2 h may take with meals distress Take without regard to

multivitamin

221

FAILURE

5

evening 6 7 pm

8

9

night 10 11 12 1 midnight

2

3

4

5 am

1. time line for assessment of drug-nutrient interactions. Instructions for use of the time an “X” through the hour to indicate waking and sleeping times. Draw a square around To record times that medication is taken, circle the time and list below the drugs that time. (Reprinted with permission.26)

222 interpretation of patient symptoms, serum drug concentrations, and clinical outcomes of therapy. Dietitians are experts at nutritional status assessment and thus provide input into the possibility of altered nutrient status as a result of a drug interaction. As a team, these health professionals can help reduce the risk of adverse consequences of drug-nutrient interactions.

REFERENCES 1. The 1994 Joint Commission Accredrtation Manual for Hospitals: Volume 1. Standards, Oakbrook Terrace, IL. Joint Commission on Accreditation of Healthcare Organizations, 1993 2 Kaplan B, Mason NA, Shimp LA, et aI, Chronic hemodialysrs patients. Part I. Charactenzatron and drug-related problems. Ann Pharmacother 28:316319,1994 3. Wrllrams L, Davis JA, Lowenthal DT. The rnfluence of food on the absorption and metabolism of drugs. Med Clin North Am 4:815-829, 1993 4. Roe DA: Diet and Drug Interactrons. New York, NY, Van Nostrand Reinhold, 1989 5 Toothaker RD, Welling PG: The effect of food on drug bioavailability. Ann Rev Pharmacol Toxicol 20 173-l 99, 1980 6. Matzke GR, Frye RF Drug dosing in patients with impaired renal function, in Diprro J, Talbert R, Hayes P, et al (eds)’ Pharmacotherapy: A Pathophystologic Approach (ed 2). Norwalk, CT, Appleton & Lange, pp 750-763,1992 7. Gibson T Influence of renal disease on pharmacokrnetics, In Evans WE, Schentag JJ, Jusko WJ (eds) Applied Pharmacokinetrcs (ed 2) Spokane, WA, Applied Therapeutics, Inc, 1986 8. Mitch WE, Jurkovitz C, England BK. Mechanisms that cause protein and amino acid catabolism in uremia. Am J Kidney Dis 21.91-95, 1993 9 Lowrie EG, Lew JD: Death risk in hemodialysis patients: The predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis 15:458482,199O 10 Lazarus JM: Nutrition in hemodralysis patients. Am J Kidney Dis 21:99-l 05, 1993

MASON 11 Maher renal failure.

JF: Pharmacokinetics Clin Nephrol21:39-46,

AND

in patients 1984

12 Welling PG. Interactions affecting tion Clin Pharmacokin 9:404-434, 1984 13 Murray JJ, Healy tions: A new responsibility Am Diet Assoc 91:66-70,73,

AR,

drug

MD: Drug-mineral for the hospital 1991

14. Lewis CW, Frongrllo EA, Roe rnteractions rn three long-term-care Diet Assoc 95 309-315,1995 15. Morton hyperphosphatemra Dial 3:219-223,

BOYD

DA

with absorp-

interacdietitian. J

Drug-nutrient facilitres J Am

Heraz G, Coburn in chronic renal

JW Control of failure. Semen

1990

16. Pinson JB, Weart CW: Antacid products, in Handbook of Nonprescription Drugs (ed 10). Washington, DC, American Pharmaceutrcal Associatron, pp 147-180,1993 17. D’Arcy PF, McElnay JC Drug the gut involvrng metal ions. Rev Drug Interact 5 83-l 12, 1985

interactions Metabol

18 Bauer L: Interference of oral phenytorn tron by continuous nasogastnc feedings 32:570-572, 1982 19 Haley CJ, Nelson J: Phenytorn-enteral interaction Ann Pharmacother 23:796-797,

in Drug

absorpNeurology feeding 1989

20. Nishrmura LY, Armstrong EP, Plezia PM, et al Influence of enteral feedings on phenytoin sodium absorption from capsules. Drug lntell Clin Pharmacol 22:130-133, 1988 21 Cutre AJ, Altman E, Lekel L. Compatrbrlity of enteral products with commonly employed drug additives J Parenter Enter Nutr 7: 186-l 91, 1983 22. Gora ML, Tschampel MM, Viscontr JA: Considerations of drug therapy in patients receiving enteral nutrition. Nutr Clin Pratt 4.105-l 10, 1989 23. Olin BR (ed). Drug Facts and Comparisons. St LOUIS, MO, Facts and Comparisons, 1994 24 Pronsky ZM (ed): Food-Medication tions (ed 8). Pottstown, PA, Food-Medrcatron tions, 1993 25 McEvoy Bethesda, MD, cists, 1994

(ed): American

AHFS Society

InteracInterac-

Drug Information. of Hospital Pharma-

26 Shimp IA, Ascrone FA: Medication (Version 5 0) Q College of Pharmacy, The of Michigan, Ann Arbor, MI, 1990

History University