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Drug Interactions


Guidelines for the Administration of Phenytoin with Enteral Feedings

The concomitant administration of phenytoin and enteral feedings results in the decreased bioavailability of phenytoin and decreased phenytoin levels. The exact mechanism of this interaction has not been found. Several factors may be involved in the reaction including gastrointestinal transit time, the nitrogen source of the feeding, the calcium content of the feeding, pH of the feeding, dosage form of phenytoin given and if the phenytoin suspension has been diluted before administration.

Although there is not just one "best" method for administering phenytoin to a tube-fed patient, these guidelines should help standardize the administration of phenytoin.

1. Basic information

a. Serum concentrations must be monitored carefully when switching a patient from the sodium salt to the free acid form or vice versa. The free acid form of phenytoin is used in the Dilantin Infatab chewables 50 mg and the Dilantin 125 mg/5 ml suspension. With the Dilantin Kapseals and phenytoin injectable 50 mg/ml, the sodium salt is used. Phenytoin sodium contains 92% phenytoin.

b. The normal serum level of phenytoin is 10-20 mg/dL. This represents the total drug concentration which consists of unbound (or free) phenytoin and phenytoin which is bound to plasma albumin. Seizure control may be achieved with lower levels or it may take higher levels than 20 to reach control.

c. The observed phenytoin concentrations must be adjusted in patients who are hypoalbuminemic.

To calculate phenytoin drug conc if serum albumin normal with normal renal fxn:

[Phenytoin] = OBSERVED PLASMA CONC/{(1-") [(patient's serum albumin in gm/dL)/(normal serum albumin in gm/dL)] + "}

"=0.1   " is the normal free fraction of phenytoin

Normal serum albumin = 4.4 gm/dL

Therefore, this equation if the patient has normal renal function becomes:

[Phenytoin] = OBSERVED PLASMA CONC/[0.2 (patient's serum albumin in gm/dL) + 0.1]

d. Concurrent administration of cimetidine, isoniazid, disulfiram, acute ethanol ingestion, sulfonamides, or omeprazole may increase phenytoin levels. Administration of barbiturates, chronic ingestion of ethanol, rifampin, and theophylline may decrease phenytoin levels. Carbamazepine effect on phenytoin is variable.

e. Phenytoin side effects such as gingival hyperplasia, folate deficiency, and peripheral neuropathy are not related to plasma phenytoin concentrations. CNS side effects do correlate with plasma concentrations and occur with concentrations greater than 20 mg/L. Monitor for ataxia, nystagmus, and diminished mental capacity.

f. IV administration of phenytoin is preferred when initiating therapy to obtain therapeutic serum concentrations. Do not exceed a rate of 50 mg/min (Refer to phenytoin adm policy ID#731-36.)

2. Oral administration of phenytoin with enteral feedings

a. If a patient has been on IV phenytoin, do not switch from IV phenytoin to suspension until therapeutic levels have been documented with the IV form. It is very difficult to rebolus phenytoin with oral suspension during concomitant enteral feeding. The injectable is only 92% phenytoin and must be converted to free acid when starting the suspension. May increase the total daily dose empirically by 25% when converting to phenytoin oral suspension with continuous feedings.

b. When changing from Dilantin capsules to phenytoin suspension, convert the total daily dose of phenytoin oral capsules to a twice daily phenytoin oral suspension regimen. Note that the capsules are 92% phenytoin (i.e. 100 mg capsules=92 mg phenytoin or 3.7 ml of phenytoin suspension 125 mg/5 ml). The 50 mg chewable infatabs does NOT have to be converted to the free acid. Single oral doses of suspension should be limited to 400 mg. May increase the total daily dose empirically by 25% when converting to phenytoin oral suspension with continuous enteral feedings.

c. Do not open the Dilantin Kapseals 100 mg for administration down a feeding tube because of its special release characteristics. Do NOT use the IV form of phenytoin for oral administration as phenytoin sodium injection is extremely hypertonic and the high pH can cause gastrointestinal cramping, distention, and possibly diarrhea.

d. Continuous tube feedings should be stopped for 1 hour before and 1 hour after each oral phenytoin dose. With a twice daily regimen the enteral nutrition feeding time will be reduced to 20 hours for achieving daily caloric goals. If the patient requires phenytoin dosing three times a day then the enteral nutrition feeding time must be altered to 18 hours for achieving daily caloric goals. (Note:The literature recommends to hold tube feedings for 2 hours before and after each dose which would require further adjustments in the enteral infusion rate or volume. In the hyper metabolic patient, it may be impossible to maintain adequate caloric intake when feedings are held for significant periods of time.) A large enteral feeding rate increase may result in intolerance such as distention or diarrhea, especially if the patient is fed into the stomach. A more calorically and protein dense formula may be required if the enteral feeding exceeds a rate of 110 ml/hr.

e. Intermittant feedings should be stopped for 2 hours before and after each phenytoin dose. Do not empirically increase the phenytoin dose by 25%, but monitor levels closely and adjust accordingly.

f. Phenytoin suspension should not be mixed with the enteral formulas because of the risk of physical incompatibilities. Flush the feeding tube with 30 ml or more of water before and after each administration to ensure tube patency. Larger bore tubes such as nasogastric or gastrostomy tubes are less likely to clog than smaller bore jejunal tubes when medications are administered through them.

g. Monitor serum levels carefully. Decrease phenytoin dose when enteral feedings are discontinued or if the enteral access is lost and parenteral phenytoin is given.

Food-drug interactions

The following 12 drugs are the most significant drugs involved in food-drug interactions in the hospital as determined by the Nutrition Support Committee. The food-drug interactions for these drugs will be discussed with patients by dietitians (except phenytoin) and documented in the history and physical section of the patient's medical chart.


















































A2 Take 2 hours after meals.

ALC Avoid alcohol and alcohol containing products (sauces, vinegar, cough syrups).

E1B2A Take without food or milk (at least 1 hour before or 2 hours after meals) to increase absorption.

F Take with food

FLUOR Avoid taking zinc & iron products (vitamins), Al & Mg products (antacids) within 4 hours before or 2 hours after dosing.

GI If GI upset occurs, take with food or after meals.

MAO Avoid ripe cheese, sausage, canned or dried meats, salami, organ meats, yeast extracts, liquid and powdered protein supplements, tofu, raspberries, wine, sauerkraut, avocado, chocolate, soy sauce, yogurt, peanuts, alcohol (beer,wine-esp chianti or hearty red wines) - to avoid possible hypertensive crisis. Procarbazine [Matulane] and Isoniazid exhibit some MAO activity. Nursing to contact dietary for consult.

TETRA Avoid iron-containing products, Al, Mg, (antacids) within 2 hours of DRUG. Avoid Ca (dairy products- milk, cheese, ice cream) with tetracycline and demeclocycline.

WARF Avoid alcohol,salicylates and drastic changes in dietary habits. Limit or maintain foods containing vitamin K; fish oils, herbal teas and green teas and green leafy vegetables (brussel sprouts, chinese cabbage, kale, cabbage, spinach, mixed greens). Limit caffeine containing beverages. Avoid megadoses of Vitamin C. Take Vitamin E only with advice of your physician. Nursing to contact dietary for consult.

Clogged feeding tubes - Also refer to nursing procedures on continuous, intermittent nasal/gastric gavage and gastrostomy/jejunostomy feedings.

Risk factors: thick feeding formulas, crushed medications, curdling of formulas from addition of low acidic substances or from bacterial contamination.

Prevention: Flush the tube with at least 20 ml of warm water:

1. after checking residuals and after each intermittent feeding

2. every 3-4 hours during continuous feeding

3. before and after the administration of medication.

Squeeze or shake the feeding container periodically for viscous formulas or for those that tend to separate.

To unclog a tube:

1. use alternate positive and negative pressure using warm water in a 30 to 60 ml syringe.

2. Coke and cranberry juice should not be used as they may cause curdling of feeding.