Medication-nutrient interactions and individuals with special healthcare needs.

[ILLUSTRATION OMITTED]

Many children and adults with special healthcare needs receive one or more medications on a regular basis. Parents and healthcare professionals who care for these individuals should be aware of each medication and potential interactions with foods/nutrients. Those who require long term or multiple medications are at highest risk for drug-nutrient interactions. The risk is compounded for those whose primary condition is associated with marginal nutritional status to begin with, due to feeding difficulties, increased energy needs, poor absorption, or impaired metabolism of nutrients. Early identification and treatment of potential medication-nutrient interactions is the best way to prevent related health problems. The registered dietitian (RD) is well qualified to evaluate such issues and to make recommendations for appropriate nutrient supplementation to avoid deficiencies (see Table 1 on page 21 for information on assessing for medication-nutrient interactions).

This article presents a discussion of the different types of medication-nutrient interactions and gives an in-depth look at anticonvulsant medications, glucocorticoids, and psychotropic medications, three classes of medications frequently prescribed for those with disabilities or chronic illnesses. Table 2 on page 22 gives a larger list of medications, their associated medication- nutrient interactions, and suggestions for assessment and intervention.

Definition of Medication-Nutrient Interactions

Medication-nutrient interactions occur any time a medication interferes with a nutrient or food or, likewise, when a food or nutrient interferes with the action of a medication. Drugs and nutrients can have a variety of interactions, which are discussed here.

1) Physical Interactions

Medications may interact with a formula or food if mixed together before administering, resulting in decreased medication and/or nutrient delivery. This can be a significant problem for children and adults dependent on tube feedings for food and medicine.

2) Absorption of a nutrient or medication

Food given with a medication may prevent, delay, or decrease the absorption of the medication. Phenytoin (Dilantin) absorption is decreased when given with food or enteral feedings. In some patients, phenytoin is always given with feedings and levels are therapeutic; in those cases, subsequent administration without feedings could result in toxic levels. Some medications bind with specific nutrients, resulting in decreased absorption of those nutrients as well as the medication. The minerals zinc, iron, calcium, and magnesium form insoluble complexes with the antibiotic tetracycline, thus, decreasing its absorption as well as the absorption of those minerals. Other drugs are most efficiently absorbed when given with food (e.g. hydrochlorithiazide). Food increases the bioavailability of the drug, which can be beneficial if always given with food but detrimental if given with food sometimes and without other times. Pharmacists' instructions for giving a medication with or without food must be taken seriously; more information can be obtained by reading the manufacturers insert or logging onto the manufacturers website.

3) Biochemical action

Many drug-nutrient interactions occur after absorption. In the late 1990s, it was found that grapefruit juice resulted in increased serum levels of drugs such as cyclosporin and calcium channel blockers (e.g. nifedipine and felodipine) and midazolam (a sedative used in pediatric dentistry). The effect of grapefruit juice lasts 24 hour, thus, it must be totally avoided for anyone regularly taking an effected drug. In some cases, serum drug levels are increased by several hundred percent. The effect varies from person to person and can be toxic in some individuals. There is ongoing research about other foods that potentially affect the metabolism of specific drugs. Many with neuromuscular or developmental disorders have seizure disorders and are treated with one or more anticonvulsants. Anticonvulsants have long been known to interfere with folic acid, vitamin D, and calcium metabolism. The evidence for these interactions is growing. Glucocorticoids are used to treat a wide variety of allergic and inflammatory diseases. They are frequently prescribed to treat conditions such as asthma, juvenile rheumatoid arthritis, nephrotic syndrome, skin conditions, and to prevent rejection of transplanted organs. It is well known that moderate to high dose, long term glucocorticoid therapy results in decreased bone mineralization due to effects on calcium absorption and excretion. Other effects include increased appetite with significant, excessive weight gain, muscle wasting, abnormal fat deposition (cushionoid effects), hyperlipidemia, sodium retention with possible hypertension, and hyperglycemia.

4) Nutritional intake

A medication may cause decreased or increased appetite, taste changes, and/or nausea and vomiting. Some antibiotics and many chemotherapy medications cause taste changes as well as nausea, thus, decreasing intake of food. Prednisone and some psychotropic drugs often cause increased appetite; the resulting increase in food intake can result in excessive weight gain and all of the issues associated with obesity. Several studies have shown that many medications used to treat ADD/ADHD result in appetite suppression and thus poor weight gain and growth.

5) Elimination of nutrients or food

A medication may cause diarrhea or constipation. With diarrhea, nutrients and fluid may be lost (e.g. many antibiotics cause diarrhea, especially in young children). Sorbitol is used as a solvent or flavoring agent in many liquid medications, and it is a common cause of diarrhea (especially in an older child who is tube fed and requires a high volume of a liquid medication to get the proper dose). A medication may result in increased urinary electrolyte losses (e.g. many diuretics cause increased urinary potassium excretion and prednisone causes increased calcium excretion). Other medications are reported by parents/caregivers to cause constipation (e.g. high doses of iron used to treat anemia).

Additional considerations

Any individual being treated with several medications at one time needs attention to nutritional intake. Medications may cause nausea or other gastrointestinal problems. Dosing of medications is often timed with meals because that is the easiest way to remember to give them. It is not uncommon for an individual to lose interest in a meal after being given a handful of medications. Many individuals with chronic illnesses are in this situation. They may have regular, long term medications with frequent, intermittent courses of antibiotics due to high frequency of infection. Patients who have had any type of organ transplant fall into this category. It is not uncommon for such a patient to be taking three anti-rejection medications one to two times per day, plus one or more anti-hypertensive medications, plus anti-viral medicines and antibiotics one to two times per day, plus supplements to deal with the drug-nutrient interactions associated with the anti-rejection medications. This medication cocktail frequently causes nausea and diarrhea, which in turn makes it very difficult for the individual to eat appropriately. He may just not eat enough and lose weight and become malnourished, or he may eat high amounts of low nutrient foods in between meals and maintain weight gain but be deficient in vitamins and minerals. See the case study below.

CASE STUDY

JP was a 10-year-old male patient with a kidney transplant who had severe hypertension. In addition to his three medications for prevention of transplant rejection, he was taking three anti-hypertensive medications. Medications were given right before meals twice a day.

JP was losing weight, and he reported poor appetite. Taking four medications right before dinner made him feel nauseous, resulting in almost no intake at dinner. Timing of medication was changed from mealtime to one to two hours after meals. This resulted in a significant increase in intake at dinner and improved weight gain. In this case the "fix" was relatively easy. A little detective work, rather than just prescribing high calorie supplements for weight loss worked well.

Summary

Many medications interfere with nutrient intake, absorption, metabolism, and/or excretion. For most people, who take medications occasionally, for limited periods of time, this is not a problem; any short term nutrient deficiencies can be quickly resolved once the medication is completed. However, for those with special needs who are on chronic medications or anyone who has frequent infections/illnesses requiring frequent short term prescriptions of antibiotics, medication-nutrient interactions become a concern. Whenever a person is seen for nutritional assessment, for any reason, he should be screened for potential medication-nutrient interactions (see Table 1). Early identification and treatment can prevent significant morbidity associated with these interactions.

See Table 2 for a list of medication-nutrient interactions associated with frequently prescribed medications for children and adults with special healthcare needs. For a more comprehensive review of medication nutrient interactions, see: Pronsky et. al., Food Medication Interactions Handbook, 14th Ed 2006, which is available from http://www.foodmedinteractions.com

By Lori S. Brizee MS, RD, LD, CSP 

Lori Brizee is a registered dietitian and certified specialist in pediatric nutrition. She has a Master's Degree in nutritional science from University of Washington, where she focused on nutrition for children with special needs. She has worked in pediatric nutrition for 25 years, including 20 years at Seattle's Children's Hospital and Regional Medical Center. She is married and has two college-aged children. Lori now lives in Bend, Oregon, where she is a private practice nutritionist.

Table 1
Assessment of Medication Nutrient Interactions

Information         Nutritional          Biochemical   Interventions
from family         assessment           assessment

Prescribed          Potential medi-      Request       Make recommen-
medications         cation-nutrient      laboratory    dations for
                    interactions         tests for     changes in diet
Complementary       with prescribed      nutrients     and/or addition
or alternative      or complementary     of concern.   of supplements
medications         or alternative                     based on
                    medications                        nutritional and
                                                       biochemical
Vitamin and         Determine adequacy                 assessment.
mineral             of nutritional
supplements         intake from diet
                    and supplements.
Typical dietary     Look especially
intake, including   for any nutrients
oral and/or         associated with
enteral intake      medications.
(food records,
food frequency
or typical
intake
interview)

Table 2
Medication-Nutrient interactions associated with medications
frequently prescribed for children with special healthcare needs

       Medications                 Use              Drug Nutrient
                                                     Interaction

Carbamazepine (Tegretol),   Anticonvulsants     Decreased folic
phentoin (Dilantin),                            acid levels with
phenybarbital, primidone                        concurrent increased
(Mysoline) Valproic Acid                        homocysteine levels.
(Depakene/Depakote

Carbamazepine (Tegretol),   Anticonvulsants     Vitamin D catabolism,
phentoin (Dilantin),                            decreased calcium
phenybarbital, primidone                        absorption, low bone
(Mysoline) Valproic Acid                        mineral density.
(Depakene/Depakote)
lamotrigine (Lamictal),
clonazepam (Rivotril,
Klonopin) gabapentin
(Neurontin) topamirate
(Topamax) and
ethosuzimide (Zarontin)

Valproic Acid/Divalproex/   Anticonvulsant,     Abnormal Carnitine
Valproate Sodium            treatment for       metabolism;
(Depakote/Depakene)         mood disorder
                            (bipolar            Weight gain, possible
                            disorder)           fluid retention with
                                                protein excretion
                                                via kidneys.

Glucocorticoids             Immuno-             Abnormal calcium and
(Prednisone,                suppressant,        vitamin D metabolism
prednisilone)               anti-inflammatory   leading to poor bone
                            agent               mineralization.

                                                Suppressed linear
                                                growth. Increased
                                                appetite leading to
                                                excessive weight
                                                gain (may not happen
                                                in children who
                                                are on multiple
                                                medications).

                                                Abnormal fat
                                                deposition
                                                (cushionoid effect)
                                                Hyperglycemia.
                                                Hyperlipidemia

                                                Sodium and fluid
                                                retention increasing
                                                risk for hypertension

methylphenidate (Ritalin,   Treatment of        Decreased appetite
Ritalin SR, Metadate CD,    Attention Deficit   leading to weight
Metadate ER, Concerta);     Hyperactivity       loss and poor
dextroamphetamine           Disorder            linear growth.
(Dexedrine); amphetamine
mixture (Adderall)
Automexetine (Strattera)

Warfarin                    anticoagulant       Decreased therapeutic
                                                action with high
                                                vitamin K in diet
                                                or with supplements
                                                containing vitamin K.

       Medications                          Comments

Carbamazepine (Tegretol),   Supplement with 400 to 1000mcg folate.
phentoin (Dilantin),        Monitor drug levels; may need to
phenybarbital, primidone    increase drug dosage with added
(Mysoline) Valproic Acid    folic acid.
(Depakene/Depakote

Carbamazepine (Tegretol),   Monitor Ca, P, Alk Phos, Vit D levels.
phentoin (Dilantin),        Supplement Vitamin D and Calcium if
phenybarbital, primidone    labs indicate deficiency. May need
(Mysoline) Valproic Acid    very large amounts of Vit D if bone
(Depakene/Depakote)         disease is severe. Monitor serum
lamotrigine (Lamictal),     calcium while high dose Vit D is given;
clonazepam (Rivotril,       if hypercalcemia, stop vit D supplement
Klonopin) gabapentin        until Ca is normalized, then re-start
(Neurontin) topamirate      at lower level.
(Topamax) and
ethosuzimide (Zarontin)

Valproic Acid/Divalproex/   Check carnitine levels and supplement
Valproate Sodium            with carnitine if levels are low.
(Depakote/Depakene)
                            If fluid retention without protein
                            excretion, instruct on low sodium diet.
                            If protein excretion, consider changing
                            to a different medication. If weight
                            gain without fluid retention, evaluate
                            diet for excessive caloric intake and
                            instruct on low fat/sugar, decreased
                            calorie diet and increased physical
                            activity according to individual

Glucocorticoids             Insure 125% of DRI for Calcium and
(Prednisone,                at least 100% DRI for Vitamin D
prednisilone)               (with diet and supplements) at time
                            initiation of drug.

                            Monitor weight, height, blood pressure,
                            blood glucose and lipids if on drug
                            for more than a few weeks.

                            Instruct on low saturated fat low
                            cholesterol, low simple sugar diet.
                            Encourage whole grains, fresh fruits
                            and vegetables. If excessive weight
                            gain, reduce total fat and sugar in
                            diet. If hypertension, decrease
                            sodium intake to 1-3 mEq per kg
                            per day. Encourage physical activity
                            as tolerated.

methylphenidate (Ritalin,   Evaluate weight gain, growth and
Ritalin SR, Metadate CD,    nutritional intake every 3 to 6 months
Metadate ER, Concerta);     while drug is being used. If signs of
dextroamphetamine           poor intake make sure nutritionally
(Dexedrine); amphetamine    dense meals and snacks are offered
mixture (Adderall)          at times when drug levels are low
Automexetine (Strattera)    (morning, before drug is given; later
                            in day when effects are waning).

Warfarin                    Maintain a consistent level of vitamin
                            K in diet; significant variations in
                            intake will increase or decrease
                            anticoagulant effect of medication.