natural medicines comprehensive database 2010

7/25/2019 Natural Medicines Comprehensive Database 2010

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Drug Influences on Nutrient Levels and Depletion


This chart was downloaded from the Nutrient Depletion Checkerin April 2010. This information changesfrequently. To get the most updated information click here to run the Nutrient Depletion Checker.


Some medications can affect the levels of certain nutrients in the body. There is considerable interest in using nutritional supplements to counteract these possible drug-induced "nutrient depletions." The chart below

shows the current scientific understanding of these relationships, and suggested actions.DRUGS(Includes some representative U.S. and Canadian Brand Names.)

NUTRIENTDEPLETED

POSSIBLEMECHANISM

COMMENTS & REFERENCES

ANALGESICS/ANTI-INFLAMMATORIES

Acetaminophen (Tylenol) Glutathione Acetaminophendepletesendogenousglutathione.

It's not known if glutathione supplements

would be beneficial.5394

Aspirin, other sa licylates Folic Acid Decreases proteinbinding and serumlevels.

Folic acid appears to be redistributedrather than lost from the body. Red bloodcell folate levels are normal.Supplements are not

needed.2677,9351,9360

Iron Mucosal damageand GI bleeding,even ifasymptomatic, cancause chronicblood loss.

Monitor for signs and symptoms ofanemia. Encourage intake of iron-richfoods since supplements may

exacerbate GI irritation.8888,9515,9576-7

V ita mi n C In cre ase s u ri na ryexcretion.

Deficiency of vitamin C is unlikely. Onlyconsider supplementation with long-termtherapy and symptoms of

deficiency.10590-2,11526-7

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Diclofenac (Voltaren), Etodolac (Lodine), Fenoprofen (Nalfon), Flurbiprofen(Ansaid), Ibuprofen (Advil, Motrin, etc), Indomethacin (Indocin), Ketoprofen (Orudis, Oruvail), Ketorolac (Toradol), Meclofenamate,Mefenamic Acid (Ponstel), Meloxicam (Mobic), Nabumetone (Relafen), Naproxen (Anaprox,Naprosyn, Naprelan), Oxaprozin(Daypro), Piroxicam (Feldene), Sulindac (Clinoril), Tolmetin (Tolectin)

Iron Mucosal damageand GI bleeding,even ifasymptomatic, cancause chronic

blood loss.

Monitor for signs and symptoms ofanemia. Encourage intake of iron-richfoods since supplements may

exacerbate GI irritation.8888,9515,9576-7

Fo li c A ci d Fo la te -d ep en de ntenzymes areinhibited by someNSAIDs.

The clinical significance of this is notknown.

ANTI-INFECTIVES

ANTIBIOTICS

Antibiotics - General :Cephalosporins, Fluoroquinolones, Isoniazid, Macrolides, Penicillins, Sulfonamides, Tetracyclines,Trimethoprim/Sulfamethoxazole

BiotinDibencozidePantothenic Acid(B5)

Destruction ofnormal intestinalmicroflora may leadto decreased

The intestinal microflora is reduced byantibiotics. However, the B vitamins aremainly obtained from the diet, and anychanges in their production by intestinal
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Pyridoxine (B6)Riboflavin (B2)Thiamine (B1)Vitamin B12Vitamin K

production ofvarious B vitaminsand vitamin K.Somecephalosporinsinterfere directlywith vitamin K-dependent clottingfactor production.

bacteria is unlikely to be clinically

significant.4434-43,6243,9502,9530

Reduction in vitamin K-dependentclotting factor production may besignificant in people with other riskfactors for low vitamin K levels. Monitorthese patients

closely.4437,4439,7135,9502,11513-6

Fo li c A ci d D isru pti on o f normal intestinalmicroflora

decreasesenterohepaticcirculation andreabsorption of folicacid, and mayreduce synthesis.Trimethopriminhibits conversionof folic acid to itsactive form.

Folic acid synthesized by intestinalmicroflora probably doesn't contributesignificantly to overall folate status, and

supplements aren't necessary with

normal courses of antibiotics.2677,4436-

7,6243Prolonged courses of high-dosetrimethoprim rarely cause megaloblasticanemia, and folic acid supplements havebeen used to prevent this. However,some evidence suggests folic acidsupplements can reduce the efficacy oftrimethoprim. Avoid supplements unlessrecommended by a

physician.2677,4468,4531,9382-7,9398-9

Aminoglycosides: Amikacin (Amikin), Gentamicin (Garamycin), Kanamycin (Kantrex), Netilmicin (Netromycin), Streptomycin,Tobramycin (Nebcin)

MagnesiumPotassium

Increased urinaryexcretion,associated with

drug-induced renaldamage.

Monitor patients for electrolytedisturbances and declining renalfunciton. Give intravenous electrolyte

replacement if necessary, and considerdose reduction/discontinuation of the

aminoglycoside. 9519

Cefditoren Pivoxil (Spectracef) Acetyl-L-CarnitineL-CarnitinePropionyl-L-Carnitine

Chronic use ofcefditoren caninduce carnitinedeficiency.

Long-term use of cefditoren mightrequire supplementation, but short-termuse does not seem to have a clinically

significant effect on carnitine levels.12759

Chloramphenicol (Chloromycetin) Niacin andNiacinamide

Chloramphenicolmay interfere withthe actions ofnicotinamideadeninedinucleotide (NAD).

Deficiency is unlikely unless therapy is

prolonged.14514,14530-3

Fluoroquinolones: Ciprofloxacin (Cipro), Enoxacin (Penetrex), Gatifloxacin (Tequin), Levofloxacin (Levaquin), Lomefloxacin

(Maxaquin), Moxifloxacin (Avelox), Norfloxacin (Noroxin), Ofloxacin (Floxin), Sparfloxacin (Zagam), Trovafloxacin (Trovan)

Calcium

IronMagnesiumZinc

Formation of

insolublecomplexes(preventsabsorption of bothnutrient andfluoroquinolone).

A significant effect on le vels of these

nutrients is unlikely whenfluoroquinolones are taken at least 2hours before, or 4-6 hours after calcium,iron, magnesium, or

zinc.828,2682,3046,4412,4531

Neomycin (Mycifradin) Beta-CaroteneDibencozideVitamin AVitamin B12

Reducedabsorption.

Not clinically significant with short-term

use of neomycin.3046,5916,8434,10565-6

Pivampicillin (Pondocillin) Acetyl-L-CarnitineL-Carnitine

Chronic use ofpivampicillin can

Long-term use of pivampicillin mightrequire supplementation, but short-term


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Propionyl-L-Carnitine

induce carnitinedeficiency.

use does not seem to have a clinically

significant effect on carnitine levels.12759

Penicillins (sodium-containing): Carbenicillin (Geocillin), Mezlocillin (Mezlin), Penicillin G sodium (Pfizerpen), Piperacillin(Pipracil), Ticarcillin (Ticar)

P ota ss iu m A l ar ge so di umload is presented tothe kidneys,resulting in sodiumreabsorption andpotassiumexcretion.

Monitor potassium levels, and givesupplements or switch to a different

antibiotic if necessary.9519

Sulfadiazine Acetyl-L-carnitineL-carnitine

Proprionyl-L-carnitine

Not known. A single case report describessymptomatic L-carnitine deficiency in a

patient treated with pyrimethamine plussulfadiazine which reversed when both

drugs were stopped.14600

Tetracyclines: Tetracycline (Achromycin V, Panmycin,Robitet, Robicaps, Sumycin,Teline, Tetracap, Tetracyn ,Tetralan),Demeclocycline (Declomycin), Doxycycline (Bio-Tab, Doryx, Doxy Caps,Doxychel, Doxychel Hyclate,Monodox, Periostat, Vibra-Tabs, Vibramycin), Minocycline (Dynacin, Vectrin), Oxytetracycline (Terramycin,Uri-Tet)

CalciumIronMagnesiumZinc

Formation ofinsolublecomplexesprevents absorptionof both nutrient andtetracycline.Doxycycline doesnot reduce zincabsorption.

A significant effect on le vels of thesenutrients is unlikely when tetracyclinesare taken at least 2 hours before, or 4-6hours after food or supplementscontaining calcium, iron, magnesium, or

zinc.4412,4531,4549-50,4945

P ota ss iu m In cre ase d r en alexcretionassociated withnephropathy.

Due to a toxic degradation product inoutdated tetracyclines. Avoid outdated

drugs.

4425

ANTIFUNGALS

Amphotericin B (Abelcet,AmBisome,Amphocin,Amphotec, Fungizone) MagnesiumPotassium

Increased urinaryexcretion,associated withdrug-induced renaldamage.

Monitor patients for electrolytedisturbances and declining renalfunction. Give intravenous electrolytereplacement if necessary, and consider

changing to a different antifungal.9519

Fluconazole (Diflucan) Potassium Increased urinaryexcretion,associated withdrug-induced renaldamage.

Monitor potassium levels and renalfunction in people on prolongedfluconazole therapy, and in those withother risk factors for hypokalemia.Consider a supplement anddiscontinuation of fluconazole if

necessary.

9519

ANTIMALARIALS

Pyrimethamine (Daraprim) Folic Acid Folate antagonism.Pyrimethaminebinds todihydrofolatereductase,preventingconversion of folicacid to its activeform.

At lower p yrimethamine do ses, the ne edfor supplementation has not beenadequately studied. Advise patients tomaintain good dietary folate intake.

People receiving larger pyrimethaminedoses (those required to treattoxoplasmosis), should receive folinicacid (leucovorin) to preventmegaloblastic anemia.


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Avoid folic acid, which antagonizes thetherapeutic effects of

pyrimethamine.4425,4532,9380

Acetyl-L-carnitineL-carnitineProprionyl-L-carnitine

Not known. A single case report describessymptomatic L-carnitine deficiency in apatient treated with pyrimethamine plussulfadiazine which reversed when both

drugs were stopped.14600

Quinacrine Riboflavin (B2) Can interfere withconversion to theactive form flavin

adeninedinubleotide (FAD).

May cause riboflavin deficiency. Clinical

significance is not known.505,10521-2

ANTIPROTAZOALS

Pentamidine (NebuPent,Pentacarinat, Pentam 300) Folic Acid Weak folateantagonist,preventingconversion of folicacid to its activeform.

Rare cases of megaloblastic anemia, butonly with prolonged parenteral therapy.Folic acid supplements are usually not

necessary.9378

Magnesi um Inc reas ed uri naryexcretion,associated withdrug-induced renaldamage.

Monitor serum magnesium levels andrenal function. Give oral or intravenous

supplements as needed.8872,9618-9

ANTIRETROVIRALS

Adefovir Acetyl-L-carnitineL-carnitineProprionyl-L-carnitine

Increased urinaryexcretion of L-carnitine.

Adefovir at d oses of 1 25-500 mg/day isassociated with significant dose- andduration-related decreases in bloodcarnitine. After 12 weeks of therapy with125-250 mg/day, decreases of 42% to

62% were seen15502 while 500 mg/daywas associated with a 66% decrease in

L-carnitine after 2 weeks.15503Somestudies used a supplement of L-carnitine500 mg/day during adefovir

therapy.15501,15504 Adefovir is now usedat a lower dose of 10 mg/day fortreatment of hepatitis B. There are no

reports of significant reductions incarnitine blood levels at this dose, andsupplements are not necessary.

Zidovudine (AZT,Combivir,Retrovir) Copper DibencozideVitamin B12Zinc

Some HIV patientstaking zidovudinehave subnormalcopper and vitaminB12 levels. Themechanism isunknown.

Preliminary data suggest lower copperlevels are not harmful and supplements

should not be used.4986,8970

Preliminary data suggest vitamin B12

supplements aren't helpful.10531-3

Zinc supplements may reduce AIDS-related opportunistic infections, but havealso been linked to increased

mortality.6565-6


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Acetyl-L-carnitineL-carnitineProprionyl-L-carnitine

Zidovudineinterferes withmitochondrialtransport of L-carnitine intomuscle cells.

Low L-carnitine blood levels are found insome people with HIV infection.Zidovudine seems to exacerbate this,and can also lower muscle carnitinelevels, which is linked to symptoms of

myopathy.3617,3618,11551 L-carnitinesupplements might improve functioningof muscle cells affected by

zidovudine,3617,9885but there are notenough data to recommend routine useof L-carnitine supplements for patientstaking zidovudine.

ANTITUBERCUL OSIS AGENTS

Aminosalicylic Acid (Para-aminosalicylic Acid, Paser) Folic Acid Inhibits absorptionin thegastrointestinaltract.

May worsen the folic acid deficiencyassociated with tuberculosis.Recommend supplements if diet is

folate-deficient.4459,8441,9363,9388,9395-

7

Iron Reducedgastrointestinalabsorption.

Monitor for signs and symptoms of irondeficiency and give supplements if

needed.9574

DibencozideVitamin B12

Reducedgastrointestinalabsorption.

Monitor vitamin B12 levels if treatmentlasts more than one

month.4558,9395,9397,9574

Cycloserine (Seromycin) Folic Acid Possibly reducesabsorption orincreasesmetabolism.

Rare cases of megaloblastic anemiareported, but usually with other factorscontributing to folate deficiency.Recommend supplements only if dietary

intake is deficient.4531,4536,9363

Niacin andNiacinamide

Interference withconversion oftryptophan toniacin.

Encephalopathy responsive toniacinamide reported rarely, usuallywhen cycloserine is used with otherdrugs which interfere with

niacin.4531,14517-8

Pyridoxine (B6) Inactivatespyridoxal-5'-phosphate,increasingpyridoxine

requirements.

Deficiency can contribute to theneurotoxicity and seizures associatedwith cycloserine. It is recommended thatpyridoxine 150-300 mg/day be taken

with cycloserine.2677,3022,4459,

8894,9501

Ethambutol (Myambutol) Copper Zinc

Ethambutol and itsmetabolite chelatecopper and zinc inthe gastrointestinaltract and decreasetheir absorption.

It is not known if copper supplementation

is beneficial.4535,8971

Zinc deficiency may contribute to visualdysfunction associated with higher dosesof ethambutol. Monitor visual function.It is not clear if zinc supplements arehelpful, and there is concern they mayinterfere with the therapeutic effects of

ethambutol.4453,11613,11639-41


6/26

Ethionamide (Trecator-SC) Niacin andNiacinamide

Ethionamide hasstructuralsimilarities toniacinamide andmay interfere withits activity.

Encephalopathy responsive toniacinamide reported rarely, usuallywhen ethionamide is used with otherdrugs which may interfere with

niacin.14517-8

Isoniazid (INH, Laniazid) Pyridoxine (B6) Interferes withpyridoxinemetabolism.

Patients receiving > 10 mg/kg/day of INHshould be supplemented with 50-100 mg

of pyridoxine per day.4481-2


Isoniazid inhibitsthe conversion of

tryptophan toniacin. It also hasstructuralsimilarities toniacinamide andmay interfere withits activity.

Might induce pellagra if taken for longperiods, particularly in poorly nourished

patients and those taking other drugswhich interfere with niacin.2677,4865-

6,6243,14514,14520

Pyrazinamide Niacin andNiacinamide

Pyrazinamide hasstructuralsimilarities toniacinamide andmay interfere withits activity.

Deficiency occurs rarely, but responds to

niacinamide supplements.14529

Rifampin (Rifadin, Rimactane,Rofact) Vitamin D Increased hepaticmetabolism of

vitamin D due toenzyme induction.

This may cause osteomalacia if therapylasts more than 1 year and vitamin D

intake is low. Monitor calcium andvitamin D levels and considersupplements if necessary. Isoniazidtaken concurrently may cause liverenzyme inhibition and prevent this

effect.11561-5

V ita mi n K Po ss ib ly d ecre ase dgastrointestinalabsorption,destruction ofvitamin K-producing bacteria,and interferencewith regeneration ofvitamin K from

inactive metabolite.

Consider supplements in people withother risk factors for vitamin K

deficiency.11517-8

ANTIVIRALS

Foscarnet (Foscavir) Magnesium Chelation andincreasedexcretion.

Monitor magnesium levels and give

supplements as necessary.8869,9617

ANTI-CANCER DRUGS

Aldesleukin (Interleukin-2, IL-2,Proleukin) Magnesium Intracellular shift of magnesium.

Supplements usually not needed. Serummagnesium levels normalize after the

course is completed.8874

Amifostine (Ethyol) Magnesium Increased urinary This is usually only a transient effect, with


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excretion. levels returning to baseline in 24

hours.9625

Busulfan Vitamin E High doses of chemotherapyseems to reducelevels of vitamin E.

The clinical significance is unknown butthere is some concern that low levelsmay increase risk of toxicity. Levels mayreturn to normal between courses. It isnot known if supplements are

helpful.98,10366,11588-9

Cisplatin (Platinol-AQ), Carboplatin (Paraplatin) Acetyl-L-carnitineL-carnitineProprionyl-L-

carnitine


Cisplatin might increase L-carnitinemobilization due to tissue injury, andreduced renal tubular reabsorption due

to renal injury. L-carnitine deficiency isunlikely in people who can maintain

adequate dietary intake.3642

Magnesi um Inc reas ed uri naryexcretion probablyassociated withdrug-induced renaldamage.

Hypomagnesemia worsens withrepeated courses of treatment, and ismore severe with cisplatin thancarboplatin. Monitor magnesium levelsand give supplements asnecessary.9626

P ota ss iu m R en al tu bu la r damage caused bycisplatin increasesloss of electrolytesincludingpotassium.

Hypokalemia is asymptomatic in manypatients, but can be associated withacute paralysis or chronic muscle

weakness.(15509,15510,15511) Monitorelectrolytes closely in patients receiving

cisplatin and use supplements whennecessary.

Vita mi n E Hi gh d ose s o f chemotherapyseems to reducelevels of vitamin E.


helpful.98,10366,11588-9

Zinc Increased urinaryexcretion.

Levels usually return to normal within 24-

48 hours after a dose.11622-3

Cyclophosphamide (Cytoxan,Neosar) Vitamin E High doses of chemotherapyseems to reducelevels of vitamin E.

The clinical significance is unknown butthere is some concern that low levelsmay increase risk of toxicity. Levels mayreturn to normal between courses. It is

not known if supplements arehelpful.98,10366,11588-9

Cytosine Arabinoside (Cytosar-U) Vitamin E High doses of chemotherapyseems to reducelevels of vitamin E.

The clinical significance is unknownthere is some concern that low levelsmay increase risk of toxicity. Levels mayreturn to normal between courses. It isnot known if supplements are

helpful.98,10366,11588-9

Dexrazoxane (Zinecard) Zinc Chelation of metalions including zinc,leading toincreased urinary

Dexrazoxane increases urinary zincexcretion 10-fold.11632 The clinicalsignificance of this is not known.


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excretion.

Doxorubicin (Adriamycin,Rubex, Doxil) Riboflavin (B2) Formation of inactive complexes,interference withbinding andconversion to activeform, increasedrenal excretion.

This might contribute to doxorubicintoxicity, but it is not known if riboflavin

supplements are helpful.9533,10528-30

Vita mi n E Hi gh d ose s o f chemotherapyseems to reduce

levels of vitamin E.

The clinical significance is unknown butthere is some concern that low levelsmay increase risk of toxicity. Levels may

return to normal between courses. It isnot known if supplements are

helpful.98,10366,11588-9

Etoposide (Etopophos,VePesid, Toposar) Vitamin E High doses of chemotherapyseems to reducelevels of vitamin E.


helpful.98,10366,11588-9

Ifosamide (Ifex) Acetyl-L-carnitineL-carnitineProprionyl-L-carnitine


This might be due to binding of L-carnitine with a metabolite of

ifosfamide.3641,11558The clinicalsignificance of this finding and the role ofL-carnitine supplements in peopletreated with ifosfamide are unknown.

Fluorouracil (5-FU,Adrucil) Niacin andNiacinamide

Interference withconversion oftryptophan toniacin.

Can cause pellagra rarely, in people withpoor nutritional intake or malabsorption.Rapidly reversed by niacin

supplements.14514,14519

Thiamine (B1) Might interfere withthe activation ofthiamine, orincrease itsbreakdown.

There isn't sufficient data to recommend

routine use of supplements.10552

Vita mi n E Hi gh d ose s o f chemotherapy mayreduce levels ofvitamin E.


helpful.98,10366,11588-9

Mercaptopurine (6-MP,Purinethol) Niacin andNiacinamide

Interferes withconversion ofniacin tonicotinamideadeninedinucleotide (NAD),due to structuralsimilarities toadenine.

May cause pellagra if high doses areused for prolonged periods (e.g., 250mg/day for 4 years). Consider

supplements as necessary.14514-5

Methotrexate (Rheumatrex) Vitamin E High doses of The clinical significance is unknown, but


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chemotherapyseems to reducelevels of vitamin E.

there is some concern that low levelsmay increase risk of toxicity. Levels mayreturn to normal between courses. It isnot known if supplements are

helpful.98,10366,11588-9

Foli c Aci d Folate antagonis t,preventingconversion of folicacid to its activeform.

Folic acid supplements can interfere withthe actions of methotrexate. Avoid,unless recommended by an

oncologist.9420

Thiotepa (Thioplex) Vitamin E High doses of

chemotherapyseems to reducelevels of vitamin E.

The clinical significance is unknown, but

there is some concern that low levelsmay increase risk of toxicity. Levels mayreturn to normal between courses. It isnot known if supplements are

helpful.98,10366,11588-9

ANTI-DIABETES AGENTS

Insulin Magnesium May increase lossof magnesium inthe urine.

Decreased absorption and osmoticdiuresis may also contribute to lowmagnesium levels in diabetic patients.The clinical significance of this effect ofinsulin is unclear. Monitor magnesium

levels.13381

Metformin (Glucophage) Folic AcidDibencozide

Vitamin B12

Malabsorption ofdietary vitamin B12

and possibly folicacid.

The Glucophage package insertrecommends obtaining hematological

parameters annually and obtaining B12levels at 2-3 year intervals in patients atincreased risk for B12deficiency.Symptomatic folic aciddeficiency is unlikely. Give supplementsonly if clinical judgment warrants

it.32,4490-1,7839,7841,8834,9520-3

Thiamine (B1) Theoretically,metformin mightreduce thiamineactivity.

This might result in more pyruvateentering the Kreb's cycle and beingconverted to lactic acid. This couldcontribute to metformin-induced lacticacidosis, but the process has not been

substantiated in humans.9536,11466

ANTIGOUT/ANTIRHEUMATIC

Azathioprine (Imuran) Niacin andNiacinamide

Azathioprine ismetabolized to 6-mercaptopurinewhich may inhibitconversion ofniacin to its activeform, nicotinamideadeninedinucleotide.

Pellagra has occurred in people withmarginal niacin status who takeazathioprine. Most people probably do

not need supplements.14513

Colchicine Beta-Carotene Disruption of intestinal mucosalfunction by

Colchicine 1-2 mg/day doesn't affectbeta-carotene serum levels, but higherdoses may. Give supplements only if


10/26

colchicine canreduce absorption.

clinical judgement warrants it.4543,5921


Disruption ofintestinal mucosalfunction bycolchicine canreduce absorption.

Colchicine 1-2 mg/day doesn't affectvitamin B12 serum levels, but higherdoses may. Monitor vitamin B12 levels inpeople taking large doses for prolongedperiods, and consider supplements if

necessary.4543-5,5921

Methotrexate (Rheumatrex) Folic Acid Folate antagonism.Binds todihydrofolate

reductase,preventingconversion of folicacid to its activeform.

In people taking long-term, low-dosemethotrexate for rheumatoid arthritis orpsoriasis, reduced folate levels increase

the risk of side effects. Recommend folicacid 1 mg/day, especially in people witha low dietary folate intake or who areexperiencing side effects. This doesn'treduce the efficacy of methotrexate in

these conditions.768,2162,4492-

4,4546,9369,9418-20People taking methotrexate for cancershould avoid folic acid supplementsunless recommended by their oncologist,since they may interfere with the

anticancer effects.9420

Penicillamine (Cuprimine,Depen) Copper IronMagnesium

Chelation in the GItract, decreasingabsorption of these

minerals.

Deficiency is unlikely unless there areother contributing factors. If supplementsare needed, separate doses from

penicillamine by at least 2hours.4453,4531,4534-5,9630

Pyridoxine (B6) Inhibition ofpyridoxine activity,possibly by formingan inactive complexwith pyridoxal-5'-phosphate.

This may contribute to peripheral andoptic neuropathy. It is recommended thatpatients treated with penicillamine forWilson's disease take pyridoxine 25mg/day. In other conditions, monitor forsigns of neuropathy, such as numbnessand tingling. Supplements of 50-150mg/day have been used when

necessary.3092,4534,8897

Zinc Chelation of zincwhich can increaseurinary zinc

excretion, but canalso increase GIabsorption of zinc.

These effects usually cancel each otherout. There are rare cases of symptomaticzinc deficiency. Use zinc supplements

only if clinicallyneeded.2678,4534,9630,11612-4

CARDIOVASCULAR

ANTIHYPERTENSIVES

Hydralazine (Apresoline) Pyridoxine (B6) Formation of aninactive complexwith pyridoxal-5'-phosphate, andincreasedexcretion.

Monitor for early signs of neuropathysuch as numbness and tingling. Give

supplements if necessary.2677,3022,4533


11/26

Captopril (Capoten) Zinc Binding of zinc,leading toincreased urinaryelimination.

Zinc depletion may contribute to tasteloss associated with captopril. Probablyonly occurs with high doses (>150mg/day) taken for prolonged periods.Routine supplements are not

necessary.25,26,6543,11618-21

CARDIAC GLYCOSIDES

Digoxin (Lanoxicaps, Lanoxin) Magnesium Reducedreabsorption ofmagnesium in therenal tube, leading

to magnesiumexcretion.

Low magnesium levels can increase therisk of arrhythmias. Hypomagnesemiamore likely with concurrent diuretic use.Monitor magnesium levels as clinical

judgment warrants and givesupplements if necessary.4556,9613,9631

CHOLESTEROL-R EDUCING DRUGS

HMG CoA Reductase Inhibitors ("Statins"):Atorvastatin (Lipitor)Fluvastatin (Lescol)Lovastatin (Mevacor)Pravastatin (Pravachol)Rosuvastatin (Crestor)Simvastatin (Zocor)

Coenzyme Q10 Blocking ofsynthesis ofmevalonic acid,which is aprecursor ofcoenzyme Q10.

Serum levels of coenzyme Q-10 arereduced but muscle levels are notaffected. Therefore, this is probably not

clinically significant.3367,3370,4404-

10,8915,1209

Bile Acid Sequestrants:Cholestyramine (LoCHOLEST,Prevalite, Questran)Colestipol (Colestid)

Beta-CaroteneVitamin AVitamin EVitamin K

Reducedabsorption of fatand fat-solublevitamins. Reduced

plasma lipids mayreduce the amountof beta caroteneand vitamins A andE carried in theblood.

Reduction in plasma beta-carotene, andvitamin A, E, and K levels is sometimesreported but levels usually remain withinnormal limits, even after several years of

treatment. Routine supplements are notnecessary. Monitor patients closely ifthey have other risk factors for

hypoprothrobinemia or bleeding.4454-

8,4460-1,5919,10566-7,11519

Folic Acid Reducedabsorption.

Low folate levels have been reported inchildren taking large doses ofcholestyramine for several months, butthe clinical significance is not clear.There are no reports of deficiency inadults. Encourage patients to maintain

good dietary intake of folate.4455,4461

Iron Reducedabsorption.

Clinically significant iron deficiency hasnot been reported. If patients need iron

supplements for other reasons, advisethem to separate doses from bile acid

sequestrants by at least 4 hours.9566


Reducedabsorption due tobinding of intrinsicfactor and vitaminB12-intrinsic factorcomplexes.

Absorption is not completely blocked.Deficiency is unlikely unless the patienthas other risk factors for vitamin B12

deficiency.4455,10542-3

CalciumVitamin D

Reducedabsorption of

Osteomalacia has occurred rarely inpeople taking high doses (e.g., >32


12/26

vitamin D, which inturn reducescalcium absorption.

g/day cholestyramine) for several years,and having other risk factors for vitaminD deficiency. Such patients may needvitamin D and calcium supplements, butmost other patients do

not.2672,4458,4460-1,5655,5809,9627

Magnesi um Pos si bl y r educ edabsorption andincreased urinarymagnesiumexcretion.

Magnesium deficiency has not beenreported.Supplements are not likely to be

needed.4096,11548,11587

Phosphate Salts Cholestyraminecan bind phosphatein the gut andreduce itsabsorption.

Cholestyramine doses of 0.2 to 1.1grams/kg/day in children and 12-16grams/day in adults have beenassociated with reduced phosphatelevels.4455,5838 Most people takingcholestyramine don't need phosphatesupplements unless their dietary intakeis low. This interaction can be avoided byseparating phosphate andcholestyramine administration by at least2 hours.

Colestipol can bindphosphate in thegut and reduce itsabsorption.

In most people taking colestipol, serumphosphate levels remain within normallimits.4460 Most people taking colestipoldon't need phosphate supplementsunless their dietary intake is low. This

interaction can be avoided by separatingphosphate and cholestyramineadministration by at least 2 hours.

Gemfibrozil (Lopid) Vitamin E Mechanismunknown.

Some studies have reported reducedserum vitamin E levels with gemfibrozil,but the clinical significance is

unknown.4096,11548,11587

Loop Diuretics:Bumetanide (Bumex, Burinex),Ethacrynic acid (Edecrin),Furosemide (Lasix),Torsemide (Demadex)

CalciumMagnesiumPotassium

Increased urinaryexcretion.

Electrolyte disturbances more likely withhigher doses. Hypokalemia andhypomagnesemia occur most commonly.May need to use potassium and/ormagnesium supplements, or add apotassium-sparing diuretic (which will

also spare magnesium).4412,9613-4,9622

Foli c Aci d Pos si bl y i nc reas edurinary excretion.

Data is very limited, and the need for folicacid supplementation has not been

adequately studied.1898

Pyr idox ine Inc reas ed uri naryexcretionpyridoxine.

Intravenous furosemide in people withchronic renal failure increases urinaryexcretion of

pyridoxine.8896,9525However, peoplewith hypertension treated with oraldiuretics for several years seem to havenormal serum pyridoxine

levels.1898 Pyridoxine supplements


13/26

aren't usually necessary.

Thiamine (B1) Increased thiamineexcretion due toincreased urinaryflow.

Thiamine deficiency may occur in elderlypeople with poor dietary intake who areon high doses of diuretics (e.g. > 80mgfurosemide/day) for several months.Thiamine deficiency may worsen heartfailure. A supplement of 200mg/day hasimproved cardiac function in some, butnot all thiamine-deficient people ondiuretics. There are not enough data torecommend routine use of

supplements.1283-6,10506-9

V ita mi n C In cre ase d u ri na rylosses of vitamin C,probably due toincreased waterexcretion.

Reported in people with chronic renalfailure who received a 20 mgintravenous dose of furosemide.Significant vitamin C depletion hasn'tbeen reported with chronic oral use of

furosemide or other diuretics.9525

Thiazide and Thiazide Derivatives:Bendroflumethiazide (Naturetin),Benzthiazide (Exna),Chlorothiazide (Diuril),Chlorthalidone (Hygroton,Thalitone),Hydrochlorothiazide (Esidrix,Hydrodiuril, Oretic),Hydroflumethiazide (Diucardin ,Saluron),Indapamide (Lozide, Lozol),Methyclothiazide (Aquatensen,Enduron),Metolazone (Mykrox,Zaroxolyn),Polythiazide (Renese),Quinethazone (Hydromox),Trichlormethiazide (Diurese,Metahydrin, Naqua)

MagnesiumPotassiumZinc

Increased urinaryexcretion.

Electrolyte disturbances are more likelywith higher doses. Hypokalemia andhypomagnesemia occur most commonly.May need to use potassium and/ormagnesium supplements, or add apotassium sparing diuretic (which will

also spare magnesium).4412,9613-4,9622

Foli c Aci d Pos si bl y i nc reas ed

urinary excretion.

Data are very limited, and the need for

folic acid supplementation has not been

adequately studied.1898

Thiamine (B1) Increased thiamineexcretion due toincreased urinaryflow.

Thiamine deficiency may occur in elderlypeople with poor dietary intake who areon high doses of diuretics for severalmonths. Thiamine deficiency mayworsen heart failure. A supplement of200 mg/day has improved cardiacfunction in some thiamine-deficientpeople on diuretics. There are notenough data to recommend routine

supplements.1283-6,10506-9

Triamterene (Dyrenium) Folic Acid Reducedabsorption of folic

acid and reducedconversion to theactive form.

Megaloblastic anemia is rare unlesspatients are on chronic therapy and have

poor dietary intake or other risk factorsfor folate deficiency. Monitor folate statusin these situation and consider

supplements if necessary.4425,4536-

7,9375

CENTRAL NERVOUS SYSTEM

ANTICONVULSANTS

Carbamazepine (Atretol, Epitol,Tegretol) Biotin Competitiveinhibition ofabsorption,increased

The clinical significance of this is notknown. It is not known if taking biotin

supplements is necessary.172,175-

6,11698-700,14501-2


14/26

breakdown, anddecreased renaltubularreabsorption.

Acetyl-L-CarnitineL-CarnitinePropionyl-L-Carnitine

Possibly increasedmetabolism ordecreasedsynthesis.

It is not known if carnitine

supplementation is necessary.1911,12758

Fo lic Aci d De cre ase dintestinalabsorption andinduction of hepaticmicrosomalenzymes leading toincreased folic acidmetabolism.

Megaloblastic anemia due to folic aciddeficiency hasn't been reported withcarbamazepine. Low folic acid levelsmight contribute to mental changes insome people on carbamazepine, butfolic acid supplements may worsenseizure control. Advise patients toconsult their physician before starting

folic acid supplements.4426-9,9359

CalciumVitamin D

Increases the rateof vitamin Dmetabolism leadingto decreased levelsof various forms ofvitamin D.Decreased vitaminD levels reducecalcium absorption.

Hypocalcemia and osteomalacia haveoccurred with long-term anticonvulsanttherapy. Advise patients takingcarbamazepine for 6 months or longer tohave their vitamin D and calcium levelschecked. Supplements may be

needed.2675,10578

V ita mi n K In du cti on o f l ive r enzymes mayincrease vitamin Kmetabolism,producing asignificantdecrease in vitaminK levels inneonates, whohaven't built upstores of thevitamin.

Increases risk of neonatal intracranialhemorrhage. Women who need to takecarbamazepine during pregnancyshould take vitamin K, 10-20 mg/day,during the last month of pregnancy. Thebaby should receive vitamin K

immediately after delivery.10582,11521-

5,11533-4

V ita mi n E C hi ld re n ta ki ngcarbamazepineseem to have lowervitamin E levelscompared tochildren notreceivingcarbamazepine.

The clinical significance is unknown. It isnot known if vitamin E supplements are

beneficial.11574-8

Phenytoin (Dilantin),Fosphenytoin (Cerebyx)

Biotin Competitiveinhibition ofabsorption,increasedbreakdown, anddecreased renaltubularreabsorption.


supplements is helpful.175-6,11698-

700,14501


15/26

Folic Acid Reducedabsorption,increasedmetabolism, andincreased demandfor folate as acoenzyme forinduced hepaticenzymes.

Folic acid supplements may reducephenytoin side effects, but can alsoreduce phenytoin serum levels and mayindependently worsen seizure control.

Advise patien ts to consult a physicianbefore starting folic acid

supplements.4427,4471,4477,4536,9354-9

Acetyl-L-CarnitineL-carnitinePropionyl-L-

Carnitine

Possibly increasedmetabolism ordecreased

synthesis.



Niacin/Niacinamide Mechanismunknown.

Case reports describe pellagra-likesymptoms with phenytoin, but this is rareand supplements are generally not

needed.14522-3

Thiamine (B1) Mechanismunknown.

Thiamine deficiency might contribute toneurologic side effects, but there isinsufficient evidence to recommend

supplements.10510-2


Reducesabsorption ofvitamin B12.

This may exacerbate the megaloblasticanemia associated with phenytoin, whichis primarily caused by folate deficiency.Encourage patients to maintainadequate dietary vitamin B12 intake.

Monitor vitamin B12 and folate if

symptoms of anemia develop.7843,10502-

5

CalciumVitamin D

Increases the rateof vitamin Dmetabolism leadingto decreased levelsof various forms ofvitamin D.Phenytoin may alsoincrease the renalexcretion of vitaminD metabolites.Decreased vitaminD levels reduce

calcium absorption.

Hypocalcemia and osteomalacia haveoccurred with long-term anticonvulsanttherapy. Advise patients taking phenytoinfor 6 months or longer that they shouldhave their vitamin D and calcium levelschecked. Supplements may be

needed.2675,4430-1,4475,10578

V ita mi n E C hi ld re n ta ki ngphenytoin seem tohave lower vitaminE levels comparedto children notreceivingphenytoin.

The clinical significance is unknown. It isnot known if vitamin E supplementats are

beneficial.11574-8

V ita mi n K In du cti on o f l ive r enzymes mayincrease vitamin Kmetabolism,

Increased risk of neonatal intracranialhemorrhage. Women who need to takephenytoin during pregnancy should takevitamin K, 10-20 mg/day, during the last


16/26

producing asignificantdecrease in vitaminK levels inneonates whohaven't built upstores of thevitamin.

month of pregnancy. The baby shouldreceive vitamin K immediately after

delivery.10582,11521-5,11533-4

Zinc May chelate zincand could reduceabsorption.

Occasional reports of reduced zinc levelsbut the clinical significance is unclearand supplements are unlikely to be

necessary.11577,11659-60,11663,11669

Phenobarbital (Luminal,Solfoton)Primidone (Mysoline)

Biotin Competitiveinhibition ofabsorption,increasedbreakdown, anddecreased renaltubularreabsorption.


supplements is helpful.172,175-6,11698-

700,14501-2

Folic Acid Reducedabsorption,increasedmetabolism, andincreased demandfor folate as acoenzyme for

induced hepaticenzymes.

Reduced folic acid levels associated withphenobarbital or primidone treatmentoccasionally lead to megaloblasticanemia, and may contribute toneurological side effects and mentalchanges. However, folic acidsupplements can worsen seizure control.

Advise patien ts to consult a physicianbefore starting folic acid

supplements.4427,4530,4536,9333,9354-9

DibecozideVitamin B12

Reducedabsorption

Encourage patients to maintainadequate dietary vitamin B12 intake.Monitor vitamin B12 status if symptoms of

anemia develop.7843,10502-5





V ita mi n E C hi ld re n ta ki ngphenobarbitalseem to have lowervitamin E levelscompared tochildren notreceivingphenobarbital.

The clinical significance is unknown. It isnot known if vitamin E supplements are

beneficial.

11574-8

CalciumVitamin D

Increased rate ofvitamin Dmetabolism leadingto decreased levelsof various forms ofvitamin D andreduced calcium

Hypocalcemia and osteomalacia canoccur with long-term anticonvulsanttherapy. Advise patients takingphenobarbital or primidone for 6 monthsor longer that they should have theirvitamin D and calcium levels checked.

Supplements may be needed.2675


17/26

absorption.

V ita mi n K In du cti on o f l ive r enzymes mayincrease vitamin Kmetabolism,producing asignificantdecrease in vitaminK levels inneonates, whohaven't built upstores of the

vitamin.

Increased risk of neonatal intracranialhemorrhage. Women who need to takethese anticonvulsants during pregnancyshould take vitamin K, 10-20 mg/day,during the last month of pregnancy. Thebaby should receive vitamin K

immediately after delivery.10582,11521-

5,1533-4

Valproic Acid (Depakene ,Depakote) Folic Acid Mechanismunknown.

Reduced levels occur occasionally, butsymptomatic folic acid deficiency has notbeen reported. Avoid supplements since

they may worsen seizure control.4427-

8,9355-6,9359



Valproic acid supplement may not benecessary in patients who have

adequate nutrition intake.1911,4528-

9,5798,9612,12758


Mechanismunknown.

There are rare case reports of deficiency,but most people do not need

supplements.14505,14523

Zinc May bind with zinc,possibly reducingserum and tissuelevels.

Data regarding the effect of valproate onzinc levels are conflicting. Some suggestthat lowered zinc levels might contributeto side effects of valproate. Most peopleare unlikely to need zinc

supplements.11652-62

Dopamine agonists

Levodopa (L-DOPA, Larodopa,Dopar) Potassium Increased urinarypotassium lossesoccur in somepeople treated withlevodopa. Themechanism isn'tclear, but the effectdoesn't occur when

a peripheraldecarboxylaseinhibitor, such ascarbidopa, is usedwith levodopa (asin Sinemet).

This interaction is unlikely to besignificant since most patients getlevodopa in combination with

carbidopa.7201

Levodopa / Cabidopa (Sinemet) Niacin andNiacinamide

Carbidopa mayreduce conversionof tryptophan toniacin.

Clinically significant niacin deficiencyhas not been reported and supplements

are unlikely to be necessary.14516

Chlorpromazine (Thorazine) Riboflavin (B2) Interference with These effects occur in animals, but there


18/26

conversion to activeform, and increasedrenal excretion.

are not enough data to know if this isclinically significant in

humans.10515,10518-21

Gastrointestinals

Antacids

Aluminum Sal ts (Amphojel,Alternajel, Basaljel, etc), Magnesium Salts (Mag-Ox, Milk of Magnesia, etc), CalciumPhosphate Salts

Aluminum sal tsbind phosphate inthe gastrointestinaltract. This reducesphosphate levels,which induces

movement ofcalcium from bonesinto the blood,increasing urinarycalcium excretion.High serummagnesium levelscan increaseurinary calciumexcretion.

Prolonged administration of large dosesof antacids may lead to hypocalcemiaand/or hypophosphatemia. Avoidprolonged administration of large doses,except when used as a phosphate

binder in patients with renal failure.2730-

1,3371,4400,4623,5979

Ch ro miu m An ta ci ds ma yreduce chromiumabsorption from thegastrointestinaltract.

Unlikely to be clinically significant.7135

Foli c Aci d Inc reas ed i ntes ti nalpH produced byantacids mayreduce folic acidabsorption.

Long-term use of large doses of antacidscan cause folate depletion if dietaryintake is very low. Most people don't

need supplements.2677,8441

Iron Increased gastricpH reduces ironsolubility andabsorption.

Unlikely to cause iron deficiency. If ironsupplements are needed for otherconditions, separate dosing times asmuch as possible. Monitor for adequate

response to iron.3046,3072,4539

GI ANTI-INFLAMMATORIES

Sulfasalazine (Azulfidine,Salazopyrin) Folic Acid Competitiveinhibition of folateabsorption, and

interference withbreakdown ofdietary folate to itsabsrobable form.Hemolysis causedby sulfasalazinecan increase folaterequirements forred blood cellformation.

Decreased folate levels are associatedwith prolonged sulfasalazine therapy,especially in doses above 2 grams/day.

This may lead to megaloblastic anemia,hyperhomocysteinemia, and anincreased risk of colon cancer in peoplewith ulcerative colitis. Recommend thatpatients increase their dietary folateintake if possible, or take a supplement,especially if they have other risk factors

for folate deficiency.2677,4515-

7,4536,4560,9353,9376-7,9379

HISTAMINE-2 BLOCKERS


19/26

H-2 Blockers:Cimetidine (Tagamet),Famotidine (Pepcid),Nizatidine (Axid),Ranitidine (Zantac)

Ca lci um Ab so rpti on o f so mecalciumsupplements,especially thecarbonate salt, isdecreased byincreased gastricpH.

There is not any evidence of a clinicallysignificant effect on calcium

levels.2738,4330-1,5060

C hro mi um In cre ase d p H ma ycause formation ofless solublechromium salts,

reducingabsorption.

The clinical significance of this is not

known.7135

Folic Acid Reducedabsorption due toincreased pH.

A significant effect on folic acid le vels isunlikely unless dietary intake is very

low.4483,8441

Iron Reduced ironabsorption from thegastrointestinaltract due toreduction in acid.

Reduction in absorption of dietary, non-heme iron occurs, but anemia is unlikelywith long-term H2-blocker use in peoplewith normal iron stores. Supplementsmay be needed in people with otherfactors contributing to iron

deficiency.4483,4539,4540-1,8876,9578


Decreased gastricacid reduces

cleavage of protein-bound dietaryvitamin B12,reducing theamount availablefor absorption.

Deficiency is unlikely unless dietaryintake of vitamin B12 is poor, or H2-

blockers are taken continuously in highdoses for 2 years or more. In thesecircumstances, monitor for vitamin B12

deficiency and anemia.4539-41,9513-

4,9528

Zinc Inhibition of gastricacid secretionmight reduceabsorption of zinc.

Clinically significant zinc depletion hasn't

been reported.11636

LAXATIVES

Mineral Oil Beta-CaroteneCalciumVitamin A

Vitamin DVitamin EVitamin K

Decreasesgastrointestinalabsorption.

Occassional use of mineral oil is unlikelyto cause deficiency. Advise patients toavoid large doses or regular use of

mineral oil.4454,4495-6

Phosphate Salts Mineral oil reducesabsorption ofvitamin D, whichacts to increasephosphateabsorption in thegastrointestinaltract andreabsorption in the

Occasional or short-term use of mineraloil isn't likely to have a clinicallysignificant effect on phosphate

levels.505,4495


20/26

kidney tubules.

Sodium Phosphates(Fleet Phospho-Soda)

MagnesiumPotassium

Increased loss ofelectrolytes fromgastrointestinaltract.

High doses (such as those used forpreoperative bowel cleansing) cancause severe electrolyte disturbances.

Avoid hig h dose s and monitor ele ctrolytelevels in the elderly and others with riskfactors for hypomagnesemia or

hypokalemia.8877,9531,9615-6

Stimulant Laxatives: Senna (Senexon, Senolax, Senokot,Senna-Gen, Senokotxtra,Black-Draught, Gentlax, Dr. CaldwellSenna, Fletcher's Castoria, Dosalax),Bisacodyl Tablets (Bisacodyl,Uniserts, Bisco-Lax, Correctol,Dulcagen , Dulcolax, Feen-a-mint, Fleet Laxative)

Po ta ssiu m Incre ase sgastrointestinallosses.

Excessive use of stimulant laxatives mayresult in hypokalemia. Limit to short-termuse of recommended doses.Hypokalemia has been reported in

patients undergoing short-term bowel-cleansing regimens. Use with caution inpatients who have other risk factors for

hypokalemia.4411-2,4425

CalciumVitamin D

Decreasesgastrointestinalabsorption.

Prolonged use of high doses of stimulantlaxatives can cause hypocalcemia andosteomalacia. Limit to short-term use of

recommened doses.11530

PANCREATIC ENZYMES

Pancreatin (Donnazyme,Pancrezyme)Pancrelipase (Cotazym, Creon,Pancrease, Ultrase, Viokase)

Folic AcidIron

Reducedabsorption due toformation ofcomplexes in thegastrointestinaltract.

Supplements may be needed withprolonged pancreatic enzyme

therapy.9374,9575,9585

PROTON PUMP INHIBITORS

Proton Pump Inhibitors: Lansoprazole (Prevacid), Omeprazole (Losec, Prilosec), Rabeprazole (Aciphex), Pantoprazole(Pantoloc,Protonix)

Beta-Carotene Increased gastricpH may decreaseabsorption of betacarotene.

Reported with a single dose of a beta-carotene supplement. Whether there is aclinically significant effect on absorption

of dietary beta cartene is unknown.31

Ca lci um Ab so rpti on o f so mecalciumsupplements,especially thecarbonate salt, isdecreased byincreased gastricpH.

There isn't any evidence of a clinicallysignificant effect on calcium

levels.2738,4330-1,5060

C hro mi um In cre ase d p H ma ycause formation ofless solublechromium salts,reducingabsorption.


known.7135

Fo li c A ci d In cre ase d p H co ul dreduce folateabsorption.

Use of PPIs for several years does notseem to cause folate deficiency.Supplements are probably not

necessary.4483,8441


21/26

Iron Reduced ironabsorption from thegastrointestinaltract due to lack ofacid.

Reduction in absorption of dietary, non-heme iron may occur, but anemia isunlikely with use of PPIs for severalyears in people with normal iron stores.Supplements may be needed in peoplewith other factors contributing to iron

deficiency.4483,4539,8850,9578


Decreased gastricacid reducescleavage of protein-bound dietaryvitamin B12,

reducing theamount availablefor absorption.

Deficiency is unlikely unless dietaryintake of vitamin B12 is poor, or PPIs aretaken continuously for 2 years or more. Itis more likely if the patient is renderedachlorhydric. In these circumstances

monitor for vitamin B12 deficiency andanemia, and consider supplements if

necessary.4483-6,9513,9528

V ita mi n C Pr el imi na ry d atasuggestsomeprazolereduces vitamin Clevels, possibly dueto increaseddestruction ofvitamin C at highergastric pH levels.

It is not known if this is clinically

significant.10572

Zinc Each 40 mg vial of pantoprazole IVcontains 1 mg

EDTA which canchelate zinc.

Pantoprazole IV 240 mg/day for 7 daysincreases urinary zinc excretion, butserum zinc levels are

unchanged.11665Zinc supplements arenot usually necessary with typical dosesof pantoprazole IV.

Inhibition of gastricacid secretionmight reduceabsorption of zinc.

PPIs might reduce absorption of zinc

from supplements,11637but PPIs don'tseem to affect zinc absorption from

food.11638Clinically significant zincdepletion has not been reported.

MISCELLANEOUS

Sucralfate Phosphate Salts Sucralfate hasphosphate bindingproperties andreduces phosphate

absorption.

Doses of 6-17 grams/day have beenused to reduce elevated phosphatelevels in patients with renal

failure.14594,14595 In people with normal

renal function there is a risk ofhypophosphatemia if large doses of 6grams/day or more are used for

prolonged periods.14595If phosphatesupplements and sucralfate are neededconcurrently, separate doses by at least2 hours.

HORMONES

Corticosteroids [Glucocorticoids]:Short-actingCortisone (Cortone), Hydrocortisone [Cortisol] (Cortef, Hydrocortone)

CalciumVitamin D

Increased renalcalcium excretionand decreased

Steroid-induced osteoporosis, and theassociated increase in fracture risk, arewell-recognized consequences of long-

I t di t ti i t ti l l i t d i i t ti f ti t id i


22/26

Intermediate-actingPrednisone (Deltasone,Meticorten, Orasone, Panasol-S), Prednisolone (Delta-Cortef,Prelone, Pediapred), Triamcinolone(Aristocort,Atolone, Kenacort), Methylprednisolone (Medrol)Long-actingDexamethasone (Decadron,Dexameth, Dexone), Betamethasone (Celestone)

intestinal calciumabsorption. Thisdepletion ofcalcium creates agreater need forvitamin D, toimprove calciumabsorption.

term administration of corticosteroids, indoses equivalent to prednisone 7.5mg/day or higher. Recommend patientsmaintain a calcium intake of 1500mg/day and a vitamin D intake of 800units/day. Monitor levels and consider

supplements if necessary.1832,4462-7

C hro mi um In cre ase s re na lexcretion ofchromium.

Chromium deficiency may contribute tocorticosteroid-induced hyperglycemia.The role of chromium supplements has

not been adequately studied.5039

Fo li c A ci d Pa ti en ts w ithmultiple sclerosistreated withmethylprednisoloneseem to havedecreased serumfolate levels.


known.9362

Magnesi um D rug- induced boneloss releasesmagnesium frombone and increasesurinary excretion.

Serum magnesium levels are usually notaffected and supplements are not

necessary.9507-9,9628-9

Potass ium C or ti costeroidscause sodiumretention, resultingin compensatoryrenal potassiumexcretion.

Hypokalemia is dose-dependent andmore common with steroids having highmineralocorticoid activity(hydrocortisone, cortisone,fludrocortisone, prednisone,prednisolone). Monitor potassium levelswith chronic therapy. If necessary, givesupplements, or switch to a steroid withno mineralocorticoid activity(betamethasone, dexamethasone,

methylprednisolone, triamcinolone).4425

S tr on ti um Mi gh t i ncre aseurinary excretion ofstrontium.


known.11405

Zinc Shift of zinc fromthe blood into thetissues and

possibly increasedloss in the urine.

Supplements are unlikely to be

necessary.11606-11

Estrogens:(Alora, Cenestin, Climara,Estinyl, Estrace, Estraderm,Estratab, FemPatch, Menest,Ogen, Premarin, Premphase,Prempro, Vivelle)

Estrogen-containing Oral Contraceptives

Fo li c A ci d Po ss ib ly re du ce dabsorption,increasedexcretion,increased proteinbinding andinduction of liverenzymes which usefolate.

Folic acid supplements should beconsidered only in people with a verylow dietary intake, or with otherconditions which contribute to folate

deficiency.4459,4498,7843-4,9371-3,9532

Magnesium Shift from plasma to Monitor magnesium levels in people with


23/26

Magnesium Shift from plasma totissues.

Monitor magnesium levels in people withother risk factors for

hypomagnesemia. 9621,9638-40

Pyridoxine (B6) Interference withpyridoxinemetabolism.

Reduced plasma pyridoxal phosphatelevels have been reported, but mayreturn to normal despite continuedtherapy, especially with low doses ofestrogen. It's suggested that pyridoxinedeficiency contributes to depression,lethargy and fatigue associated with oralcontraceptives, but there is no goodevidence that supplements

help.4459,4498,9504-6,9510

Riboflavin (B2) Possibly reducedabsorption orinterference withconversion to activeform.

Reduced riboflavin levels reported inwomen with low dietary intake who weretaking high-dose oral contraceptiveswhich are no longer available. Riboflavinsupplements are not necessary whendietary intake is

adequate.4548,9373,9505,10523-7,10536

Thiamine (B1) Small reduction inactivity of thethiamine-dependent enzymeerythrocytetransketolase,suggesting mild

thiamine deficiency.

Routine use of thiamine supplements is

not necessary.10548,10555

Vitamin A Estr ogens s ti mulateproduction of retinolbinding protein,increasing theamount of vitamin Aremoved from liverstorage and carriedin blood.

Vitamin A supplements might helpmaintain liver stores, but the need for thishasn't been

proven.9373,9505,10523,10548


Reduced proteinbinding, leading toincreased tissueuptake.

Vitamin B12 supplements are not

necessary.4498,4547,7843,9371-

3,9505,10123

Vitamin C May reduce

absorption,increasebreakdown, orincrease vitamin Crequirements toprevent oxidation ofestrogens.

Data are conflicting, but deficiency is

unlikely unless dietary vitamin C is verylow. Routine supplements are not

necessary.10548,10583,10585-

7,11161,11528,11875-6

Zinc Decreases inserum albumin mayreduce the amountof zinc carried inthe blood. There

Data are conflicting, but there does notappear to be increased loss of zinc fromthe body. Supplements are probably not

necessary.9505,11642-51

may also be


24/26

may also beincreased use anduptake of zinc bythe tissues due toanabolic effects.

Thyroid hormones:Levothyroxine (Levothroid,Levoxyl, Synthroid, Thyro-Tabs,Unithroid)Thyroid desiccated (Armour Thyroid)Liothyronine sodium (Cytomel)

Calcium Increased boneturnover may leadto increased urinarycalcium losses.

Calcium loss is unlikely to be clinicallysignificant with doses of thyroidhormones used to treat hypothyroidism.Check thyroid function tests to ensurepatients are not receiving excessivethyroid hormone doses, which may

increase calcium losses.27-9,2684-

5,2695,2697-8,2721

Teriparatide (Forteo) Phosphate Salts Teriparatideincreases urinaryphosphateexcretion anddecreases serumphosphate similarlyto humanparathyroidhormone.

After a single dose of teriparatide, serumphosphate levels fall for about 2 hours

and then recover to baseline.14590Thisrecovery also seems to continue evenwith several years of treatment, withpatients having either no change inserum phosphate levels, or a smalldecrease which does not take thembelow the normal

range.14596,14597,14598,14599 Phosphatesupplements are not necessary withteriparatide.

RESPIRATORY

Beta-2-Agonists:Albuterol (salb utamol, Proventil,Ventolin), Bitolterol (Tornalate), Isoetharine, Levalbuterol (Xopenex), Metaproterenol (Alupent),Pirbuterol (Maxair), Salmeterol (Serevent), Terbutaline (Brethine)

MagnesiumPotassium Intracellular shift ofmagnesium andpotassium.

May contribute to arrhythmias, especiallyat high doses and in people with otherrisk factors. Monitor electrolyte levelsduring acute use of high doses (e.g., inpreterm labor or acute asthma attacks),and in people with other risk factors. Withchronic use of beta-2-agonists,electrolyte levels may return to

baseline.2644,6203,6205,6209-

10,6217,7001,8880-6, 8889-

91,9507,9517,9534,9599,9641

MethylxanthinesTheophylline (Slobid, Theo-24,Theo-Dur, Theolair)

AminophyllineOxtriphylline (Choledyl SA)

Diphylline (Lufyllin)

Potass ium Pos si bl y i nc reas edintracellular uptake.

Risk for hypokalemia is dose-dependent.Monitor potassium levels in people onhigh doses or with other risk

factors.9534,9537-9

Pyridoxine (B6) Inhibits conversionof pyridoxine to itsactive form.

Suggested that pyridoxine deficiencycontributes to side effects of theophylline,but data are conflicting. It is not clearwhether there is any benefit withpyridoxine

supplements.4522,7064,7066,9480,9503

MISCELLANEOUS

Alcohol Glutathione Alcohol d epletesendogenousglutathione.

It is not known if glutathione supplementswould be beneficial.

Cobalt Irradiation Dibencozide Irradiation of the The clinical significance is unknown 15


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Cobalt Irradiation DibencozideVitamin B12

Irradiation of thesmall bowel candecreaseabsorption ofvitamin B12.

The clinical significance is unknown.

Cyclosporine (Neoral,Sandimmune) Magnesium Significant loss of magnesium in theurine, probably dueto reduced tubularreabsorption andtubular damage.

Hypomagnesemia may contribute toseizures and neurotoxicity. Monitorserum magnesium levels closely.Supplements may be needed, or dosereduction/discontinuation of

cyclosporine.9117,9632-3

Deferoxamine (Desferal) Zinc Dose-dependent

increase in urinaryzinc elimination.

Some people maintain normal zinc

levels due to compensatory mechanismswhile others do not. Deficiency is rare,but may be linked to visual/hearing loss.Monitor for zinc deficiency and give

supplements if necessary.6597,11628-31

Disulfiram (Antabuse) Zinc A metabolite of disulfiram chelateszinc, altering zincabsorption.

Doses of disulfiram up to about 320mg/day may decrease intestinal zincabsorption, while higher doses of 400mg/day might increase it

slightly.11613,11635 The clinicalsignificance of this is not clear.

EDTA Zinc Chelation of metalions, including zinc,leading to

increased urinaryexcretion.

In the treatment of lead poisoning,calcium disodium EDTA increasesurinary zinc excretion 10- to 17-fold, and

decreases serum levels 40%. Levelsrecover after a single course, butrepeated courses can cause deficiency.There is concern that supplements mayreduce efficacy of EDTA treatment. Use

only if clinically necessary.9630,11667-

8,11670

Isotretinoin (Accutane, Claravis,Accutane Roche , Isotrex) Acetyl-L-carnitineL-carnitineProprionyl-L-carnitine

Not known. Reduced carnitine blood levels havebeen reported, sometimes withsymptoms of carnitine deficiency, suchas myalgia and muscle

stiffness.3619Other studies have foundno significant effect of isotretinoin on

carnitine blood levels.11557There is notenough information to recommend

routine use of L-carnitine supplementswith isotretinoin.

Lanthanum Carbonate Phosphate Salts Lanthanumcarbonate bindsphosphate in thegut and reduce isabsorption.

Lanthanum carbonate is usedtherapeutically to reduce elevatedphosphate levels in patients with renal

failure.14588 Avoid lanthanum carbonatein people with normal phosphate levels.

Nitrous oxide (N2O) DibencozideVitamin B12

Inactivates thecobalamin form ofvitamin B12.

Deficiency symptoms may occur after asingle dose of nitrous oxide in peoplewith pre-existing, subclinical deficiency.Check vitamin B12 levels before using

nitrous oxide anesthesia in people with


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p prisk factors for vitamin B12

deficiency.9527,9532

Orlistat (Xenical) Beta-CaroteneVitamin AVitamin DVitamin EVitamin K

Decreasedabsorption of fatsoluble vitaminsfrom thegastrointestinaltract.

Vitamin levels usually remain withinnormal limits. The manufacturer of orlistatrecommends all patients take amultivitamin supplement, separating thedose from orlistat by a least 2 hours.Monitor clotting times closely in patientstaking warfarin and

orlistat.1727,1730,9595,10570-1,11520

Sevelamer Phosphate Salts Sevelamer binds

phosphate in thegut by an ionexchangemechanism.

Sevelamer is used to reduce elevated

phosphate levels in patients with renalfailure. Avoid sevelamer in people with

normal phosphate levels.14588

Sunscreens Vitamin D Frequent andextensiveapplication ofsunscreens canreduce vitamin Dsynthesis in theskin and plasmalevels.

Usual use of sunscreen is not likely tocause clinically significant vitamin D

deficiency in most people.11507-9

Tacrolimus (FK506, Prograf) Magnesium Reduced renaltubularreabsorption leadsto increasedexcretion ofmagnesium.

Hypomagnesemia occurs in a significantproportion of patients. Monitor levels andgive supplements as

necessary.8900,9620

Footnote: Oral L-carnitine supplementation is strongly suggested for the following groups: patients with certain secondary carnitine deficiency syndromes symptomatic VPA-associated hyperammonemia multiplerisk factors for VPA-associated hepatotoxicity infants and young children taking VPA. An oral L-carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day has been recommended.

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