Drug Influences Nutrient Levels Depletion

Drug Influences on Nutrient Levels and Depletion

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.)

NUTRIENT DEPLETED

POSSIBLE MECHANISM

COMMENTS & REFERENCES

ANALGESICS/ANTI-INFLAMMATORIES

Acetaminophen (Tylenol) Glutathione Acetaminophen depletes endogenous glutathione.

It's not known if glutathione supplements would be beneficial.5394

Aspirin, other salicylates Folic Acid Decreases protein binding and serum levels.

Folic acid appears to be redistributed rather than lost from the body. Red blood cell folate levels are normal. Supplements are not needed.2677,9351,9360

Iron Mucosal damage and GI bleeding, even if asymptomatic, can cause chronic blood loss.

Monitor for signs and symptoms of anemia. Encourage intake of iron-rich foods since supplements may exacerbate GI irritation.8888,9515,9576-7

Vitamin C Increases urinary excretion.

Deficiency of vitamin C is unlikely. Only consider supplementation with long-term therapy 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,

Iron Mucosal damage and GI bleeding, even if asymptomatic, can cause chronic blood loss.

Monitor for signs and symptoms of anemia. Encourage intake of iron-rich foods since supplements may exacerbate GI irritation.8888,9515,9576-7

Folic Acid Folate-dependent enzymes are inhibited by some NSAIDs.

The clinical significance of this is not known.

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Mefenamic Acid (Ponstel), Meloxicam (Mobic), Nabumetone (Relafen), Naproxen (Anaprox, Naprosyn, Naprelan), Oxaprozin (Daypro), Piroxicam (Feldene), Sulindac (Clinoril), Tolmetin (Tolectin)

ANTI-INFECTIVES

ANTIBIOTICS

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

Biotin Dibencozide Pantothenic Acid (B5) Pyridoxine (B6) Riboflavin (B2) Thiamine (B1) Vitamin B12 Vitamin K

Destruction of normal intestinal microflora may lead to decreased production of various B vitamins and vitamin K. Some cephalosporins interfere directly with vitamin K-dependent clotting factor production.

The intestinal microflora is reduced by antibiotics. However, the B vitamins are mainly obtained from the diet, and any changes in their production by intestinal bacteria is unlikely to be clinically significant.4434-43,6243,9502,9530 Reduction in vitamin K-dependent clotting factor production may be significant in people with other risk factors for low vitamin K levels. Monitor these patients closely.4437,4439,7135,9502,11513-6

Folic Acid Disruption of normal intestinal microflora decreases enterohepatic circulation and reabsorption of folic acid, and may reduce synthesis. Trimethoprim inhibits conversion of folic acid to its active form.

Folic acid synthesized by intestinal microflora probably doesn't contribute significantly to overall folate status, and supplements aren't necessary with normal courses of antibiotics.2677,4436-7,6243 Prolonged courses of high-dose trimethoprim rarely cause megaloblastic anemia, and folic acid supplements have been used to prevent this. However, some evidence suggests folic acid

supplements can reduce the efficacy of trimethoprim. Avoid supplements unless recommended by a physician.2677,4468,4531,9382-

7,9398-9

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

Magnesium Potassium

Increased urinary excretion, associated with drug-induced renal damage.

Monitor patients for electrolyte disturbances and declining renal funciton. Give intravenous electrolyte replacement if necessary, and consider dose reduction/discontinuation of the aminoglycoside.9519

Cefditoren Pivoxil (Spectracef)

Acetyl-L-Carnitine L-Carnitine Propionyl-L-Carnitine

Chronic use of cefditoren can induce carnitine deficiency.

Long-term use of cefditoren might require supplementation, but short-term use does not seem to have a clinically significant effect on carnitine levels.12759

Chloramphenicol (Chloromycetin)

Niacin and Niacinamide

Chloramphenicol may interfere with the actions of nicotinamide adenine dinucleotide (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 Iron Magnesium Zinc

Formation of insoluble complexes (prevents absorption of both nutrient and fluoroquinolone).

A significant effect on levels of these nutrients is unlikely when fluoroquinolones are taken at least 2 hours before, or 4-6 hours after calcium, iron, magnesium, or zinc. 828,2682,3046,4412,4531

Neomycin (Mycifradin) Beta-Carotene Dibencozide Vitamin A Vitamin B12

Reduced absorption.

Not clinically significant with short-term use of neomycin.3046,5916,8434,10565-6

Pivampicillin (Pondocillin) Acetyl-L-Carnitine L-Carnitine Propionyl-L-Carnitine

Chronic use of pivampicillin can induce carnitine deficiency.

Long-term use of pivampicillin might require supplementation, but short-term 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)

Potassium A large sodium load is presented to the kidneys, resulting in sodium reabsorption and potassium excretion.

Monitor potassium levels, and give supplements or switch to a different antibiotic if necessary.9519

Sulfadiazine Acetyl-L-carnitine L-carnitine Proprionyl-L-carnitine

Not known. A single case report describes symptomatic L-carnitine deficiency in a patient treated with pyrimethamine plus sulfadiazine 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)

Calcium Iron Magnesium Zinc

Formation of insoluble complexes prevents absorption of both nutrient and tetracycline. Doxycycline does not reduce zinc absorption.

A significant effect on levels of these nutrients is unlikely when tetracyclines are taken at least 2 hours before, or 4-6 hours after food or supplements containing calcium, iron, magnesium, or zinc.4412,4531,4549-50,4945

Potassium Increased renal excretion associated with nephropathy.

Due to a toxic degradation product in outdated tetracyclines. Avoid outdated drugs.4425

ANTIFUNGALS

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

Magnesium Potassium

Increased urinary excretion, associated with drug-induced renal damage.

Monitor patients for electrolyte disturbances and declining renal function. Give intravenous electrolyte replacement if necessary,

and consider changing to a different antifungal.9519

Fluconazole (Diflucan) Potassium Increased urinary excretion, associated with drug-induced renal damage.

Monitor potassium levels and renal function in people on prolonged fluconazole therapy, and in those with other risk factors for hypokalemia. Consider a supplement and discontinuation of fluconazole if necessary.9519

ANTIMALARIALS

Pyrimethamine (Daraprim) Folic Acid Folate antagonism. Pyrimethamine binds to dihydrofolate reductase, preventing conversion of folic acid to its active form.

At lower pyrimethamine doses, the need for supplementation has not been adequately studied. Advise patients to maintain good dietary folate intake. People receiving larger pyrimethamine doses (those required to treat toxoplasmosis), should receive folinic acid (leucovorin) to prevent megaloblastic anemia. Avoid folic acid, which antagonizes the therapeutic effects of pyrimethamine.4425,4532,9380

Acetyl-L-carnitine L-carnitine Proprionyl-L-carnitine

Not known. A single case report describes symptomatic L-carnitine deficiency in a patient treated with pyrimethamine plus sulfadiazine which reversed when both drugs were stopped.14600

Quinacrine Riboflavin (B2) Can interfere with conversion to the active form flavin adenine dinubleotide (FAD).

May cause riboflavin deficiency. Clinical significance is not known.505,10521-2

ANTIPROTAZOALS

Pentamidine (NebuPent, Pentacarinat, Pentam 300)

Folic Acid Weak folate antagonist, preventing conversion of folic acid to its active form.

Rare cases of megaloblastic anemia, but only with prolonged parenteral therapy. Folic acid supplements are usually not necessary.9378

Magnesium Increased urinary excretion, associated with drug-induced renal damage.

Monitor serum magnesium levels and renal function. Give oral or intravenous supplements as needed.8872,9618-9

ANTIRETROVIRALS

Adefovir Acetyl-L-carnitine L-carnitine Proprionyl-L-carnitine

Increased urinary excretion of L-carnitine.

Adefovir at doses of 125-500 mg/day is associated with significant dose- and duration-related decreases in blood carnitine. After 12 weeks of therapy with 125-250 mg/day, decreases of 42% to 62% were seen;15502 while 500 mg/day was associated with a 66% decrease in L-carnitine after 2 weeks.15503 Some studies used a supplement of L-carnitine 500 mg/day during adefovir therapy.15501,15504 Adefovir is now used at a lower dose of 10 mg/day for treatment of hepatitis B. There are no reports of significant reductions in carnitine blood levels at this dose, and supplements are not necessary.

Zidovudine (AZT, Combivir, Retrovir)

Copper Dibencozide Vitamin B12 Zinc

Some HIV patients taking zidovudine have subnormal copper and vitamin B12 levels. The mechanism is

Preliminary data suggest lower copper levels 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

unknown. reduce AIDS-related opportunistic infections, but have also been linked to increased mortality.6565-6


Zidovudine interferes with mitochondrial transport of L-carnitine into muscle cells.

Low L-carnitine blood levels are found in some people with HIV infection. Zidovudine seems to exacerbate this, and can also lower muscle carnitine levels, which is linked to symptoms of myopathy.3617,3618,11551 L-carnitine supplements might improve functioning of muscle cells affected by zidovudine,3617,9885 but there are not enough data to recommend routine use of L-carnitine supplements for patients taking zidovudine.

ANTITUBERCULOSIS AGENTS

Aminosalicylic Acid (Para-aminosalicylic Acid, Paser)

Folic Acid Inhibits absorption in the gastrointestinal tract.

May worsen the folic acid deficiency associated with tuberculosis. Recommend supplements if diet is folate-deficient.4459,8441,9363,9388,9395-

7

Iron Reduced gastrointestinal absorption.

Monitor for signs and symptoms of iron deficiency and give supplements if needed.9574

Dibencozide Vitamin B12

Reduced gastrointestinal absorption.

Monitor vitamin B12 levels if treatment lasts more than one month.4558,9395,9397,9574

Cycloserine (Seromycin) Folic Acid Possibly reduces absorption or increases metabolism.

Rare cases of megaloblastic anemia reported, but usually with other factors contributing to folate deficiency. Recommend supplements only if dietary intake is deficient.4531,4536,9363


Interference with conversion of tryptophan to niacin.

Encephalopathy responsive to niacinamide reported rarely, usually when cycloserine is used with other drugs which interfere with niacin.4531,14517-8

Pyridoxine (B6) Inactivates pyridoxal-5'-phosphate, increasing pyridoxine requirements.

Deficiency can contribute to the neurotoxicity and seizures associated with cycloserine. It is recommended that pyridoxine 150-300 mg/day be taken with cycloserine.2677,3022,4459,

8894,9501

Ethambutol (Myambutol) Copper Zinc

Ethambutol and its metabolite chelate copper and zinc in the gastrointestinal tract and decrease their absorption.

It is not known if copper supplementation is beneficial.4535,8971 Zinc deficiency may contribute to visual dysfunction associated with higher doses of ethambutol. Monitor visual function. It is not clear if zinc supplements are helpful, and there is concern they may interfere with the therapeutic effects of ethambutol.4453,11613,11639-41

Ethionamide (Trecator-SC) Niacin and Niacinamide

Ethionamide has structural similarities to niacinamide and may interfere with its activity.

Encephalopathy responsive to niacinamide reported rarely, usually when ethionamide is used with other drugs which may interfere with niacin.14517-8

Isoniazid (INH, Laniazid) Pyridoxine (B6) Interferes with pyridoxine metabolism.

Patients receiving > 10 mg/kg/day of INH should be supplemented with 50-100 mg of pyridoxine per day.4481-2


Isoniazid inhibits the conversion of tryptophan to

Might induce pellagra if taken for long periods, particularly in poorly

niacin. It also has structural similarities to niacinamide and may interfere with its activity.

nourished patients and those taking other drugs which interfere with niacin.2677,4865-

6,6243,14514,14520

Pyrazinamide Niacin and Niacinamide

Pyrazinamide has structural similarities to niacinamide and may interfere with its activity.

Deficiency occurs rarely, but responds to niacinamide supplements.14529

Rifampin (Rifadin, Rimactane, Rofact)

Vitamin D Increased hepatic metabolism of vitamin D due to enzyme induction.

This may cause osteomalacia if therapy lasts more than 1 year and vitamin D intake is low. Monitor calcium and vitamin D levels and consider supplements if necessary. Isoniazid taken concurrently may cause liver enzyme inhibition and prevent this effect.11561-5

Vitamin K Possibly decreased gastrointestinal absorption, destruction of vitamin K-producing bacteria, and interference with regeneration of vitamin K from inactive metabolite.

Consider supplements in people with other risk factors for vitamin K deficiency.11517-8

ANTIVIRALS

Foscarnet (Foscavir) Magnesium Chelation and increased excretion.

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. Serum magnesium

levels normalize after the course is completed.8874

Amifostine (Ethyol) Magnesium Increased urinary excretion.

This is usually only a transient effect, with levels returning to baseline in 24 hours.9625

Busulfan Vitamin E High doses of chemotherapy seems to reduce levels of vitamin E.

The clinical significance is unknown; but there is some concern that low levels may increase risk of toxicity. Levels may return to normal between courses. It is not known if supplements are helpful.98,10366,11588-9

Cisplatin (Platinol-AQ), Carboplatin (Paraplatin)



Cisplatin might increase L-carnitine mobilization due to tissue injury, and reduced renal tubular reabsorption due to renal injury. L-carnitine deficiency is unlikely in people who can maintain adequate dietary intake.3642

Magnesium Increased urinary excretion probably associated with drug-induced renal damage.

Hypomagnesemia worsens with repeated courses of treatment, and is more severe with cisplatin than carboplatin. Monitor magnesium levels and give supplements as necessary.9626

Potassium Renal tubular damage caused by cisplatin increases loss of electrolytes including potassium.

Hypokalemia is asymptomatic in many patients, but can be associated with acute paralysis or chronic muscle weakness.(15509,15510,15511) Monitor electrolytes closely in patients receiving cisplatin and use supplements when necessary.

Vitamin E High doses of The clinical significance is

chemotherapy seems to reduce levels of vitamin E.

unknown; but there is some concern that low levels may increase risk of toxicity. Levels may return to normal between courses. It is not known if supplements are helpful.98,10366,11588-9

Zinc Increased urinary excretion.

Levels usually return to normal within 24-48 hours after a dose.11622-3

Cyclophosphamide (Cytoxan, Neosar)

Vitamin E High doses of chemotherapy seems to reduce levels of vitamin E.


Cytosine Arabinoside (Cytosar-U)


The clinical significance is unknown; there is some concern that low levels may increase risk of toxicity. Levels may return to normal between courses. It is not known if supplements are helpful.98,10366,11588-9

Dexrazoxane (Zinecard) Zinc Chelation of metal ions including zinc, leading to increased urinary excretion.

Dexrazoxane increases urinary zinc excretion 10-fold.11632 The clinical significance of this is not known.

Doxorubicin (Adriamycin, Rubex, Doxil)

Riboflavin (B2) Formation of inactive complexes, interference with binding and conversion to active form, increased renal excretion.

This might contribute to doxorubicin toxicity, but it is not known if riboflavin supplements are helpful.9533,10528-30

Vitamin E High doses of chemotherapy

The clinical significance is unknown; but there is some

seems to reduce levels of vitamin E.

concern that low levels may increase risk of toxicity. Levels may return to normal between courses. It is not known if supplements are helpful.98,10366,11588-9

Etoposide (Etopophos, VePesid, Toposar)



Ifosamide (Ifex) Acetyl-L-carnitine L-carnitine Proprionyl-L-carnitine


This might be due to binding of L-carnitine with a metabolite of ifosfamide.3641,11558 The clinical significance of this finding and the role of L-carnitine supplements in people treated with ifosfamide are unknown.

Fluorouracil (5-FU, Adrucil) Niacin and Niacinamide

Interference with conversion of tryptophan to niacin.

Can cause pellagra rarely, in people with poor nutritional intake or malabsorption. Rapidly reversed by niacin supplements.14514,14519

Thiamine (B1) Might interfere with the activation of thiamine, or increase its breakdown.

There isn't sufficient data to recommend routine use of supplements.10552

Vitamin E High doses of chemotherapy may reduce levels of vitamin E.


Mercaptopurine (6-MP, Niacin and Interferes with May cause pellagra if high

Purinethol) Niacinamide conversion of niacin to nicotinamide adenine dinucleotide (NAD), due to structural similarities to adenine.

doses are used for prolonged periods (e.g., 250 mg/day for 4 years). Consider supplements as necessary.14514-5

Methotrexate (Rheumatrex) Vitamin E High doses of chemotherapy seems to reduce levels of vitamin E.

The clinical significance is unknown, but there is some concern that low levels may increase risk of toxicity. Levels may return to normal between courses. It is not known if supplements are helpful.98,10366,11588-9

Folic Acid Folate antagonist, preventing conversion of folic acid to its active form.

Folic acid supplements can interfere with the actions of methotrexate. Avoid, unless recommended by an oncologist.9420

Thiotepa (Thioplex) Vitamin E High doses of chemotherapy seems to reduce levels of vitamin E.

The clinical significance is unknown, but there is some concern that low levels may increase risk of toxicity. Levels may return to normal between courses. It is not known if supplements are helpful.98,10366,11588-9

ANTI-DIABETES AGENTS

Insulin Magnesium May increase loss of magnesium in the urine.

Decreased absorption and osmotic diuresis may also contribute to low magnesium levels in diabetic patients. The clinical significance of this effect of insulin is unclear. Monitor magnesium levels.13381

Metformin (Glucophage) Folic Acid Dibencozide

Malabsorption of dietary vitamin

The Glucophage package insert recommends

Vitamin B12 B12 and possibly folic acid.

obtaining hematological parameters annually and obtaining B12 levels at 2-3 year intervals in patients at increased risk for B12 deficiency.Symptomatic folic acid deficiency is unlikely. Give supplements only if clinical judgment warrants it.32,4490-

1,7839,7841,8834,9520-3

Thiamine (B1) Theoretically, metformin might reduce thiamine activity.

This might result in more pyruvate entering the Kreb's cycle and being converted to lactic acid. This could contribute to metformin-induced lactic acidosis, but the process has not been substantiated in humans.9536,11466

ANTIGOUT/ANTIRHEUMATIC

Azathioprine (Imuran) Niacin and Niacinamide

Azathioprine is metabolized to 6-mercaptopurine which may inhibit conversion of niacin to its active form, nicotinamide adenine dinucleotide.

Pellagra has occurred in people with marginal niacin status who take azathioprine. Most people probably do not need supplements.14513

Colchicine Beta-Carotene Disruption of intestinal mucosal function by colchicine can reduce absorption.

Colchicine 1-2 mg/day doesn't affect beta-carotene serum levels, but higher doses may. Give supplements only if clinical judgement warrants it.4543,5921


Disruption of intestinal mucosal function by colchicine can reduce

Colchicine 1-2 mg/day doesn't affect vitamin B12 serum levels, but higher doses may. Monitor vitamin B12 levels in people taking

absorption. large doses for prolonged periods, and consider supplements if necessary.4543-5,5921

Methotrexate (Rheumatrex) Folic Acid Folate antagonism. Binds to dihydrofolate reductase, preventing conversion of folic acid to its active form.

In people taking long-term, low-dose methotrexate for rheumatoid arthritis or psoriasis, reduced folate levels increase the risk of side effects. Recommend folic acid 1 mg/day, especially in people with a low dietary folate intake or who are experiencing side effects. This doesn't reduce the efficacy of methotrexate in these conditions.768,2162,4492-

4,4546,9369,9418-20 People taking methotrexate for cancer should avoid folic acid supplements unless recommended by their oncologist, since they may interfere with the anticancer effects.9420

Penicillamine (Cuprimine, Depen)

Copper Iron Magnesium

Chelation in the GI tract, decreasing absorption of these minerals.

Deficiency is unlikely unless there are other contributing factors. If supplements are needed, separate doses from penicillamine by at least 2 hours.4453,4531,4534-5,9630

Pyridoxine (B6) Inhibition of pyridoxine activity, possibly by forming an inactive complex with pyridoxal-5'-phosphate.

This may contribute to peripheral and optic neuropathy. It is recommended that patients treated with penicillamine for Wilson's disease take pyridoxine 25 mg/day. In other conditions, monitor for signs of neuropathy, such as numbness and tingling. Supplements of 50-150 mg/day have been used

when necessary.3092,4534,8897

Zinc Chelation of zinc which can increase urinary zinc excretion, but can also increase GI absorption of zinc.

These effects usually cancel each other out. There are rare cases of symptomatic zinc deficiency. Use zinc supplements only if clinically needed.2678,4534,9630,11612-4

CARDIOVASCULAR

ANTIHYPERTENSIVES

Hydralazine (Apresoline) Pyridoxine (B6) Formation of an inactive complex with pyridoxal-5'-phosphate, and increased excretion.

Monitor for early signs of neuropathy such as numbness and tingling. Give supplements if necessary.2677,3022,4533

Captopril (Capoten) Zinc Binding of zinc, leading to increased urinary elimination.

Zinc depletion may contribute to taste loss associated with captopril. Probably only occurs with high doses (>150 mg/day) taken for prolonged periods. Routine supplements are not necessary.25,26,6543,11618-21

CARDIAC GLYCOSIDES

Digoxin (Lanoxicaps, Lanoxin)

Magnesium Reduced reabsorption of magnesium in the renal tube, leading to magnesium excretion.

Low magnesium levels can increase the risk of arrhythmias. Hypomagnesemia more likely with concurrent diuretic use. Monitor magnesium levels as clinical judgment warrants and give supplements if necessary.4556,9613,9631

CHOLESTEROL-REDUCING DRUGS

HMG CoA Reductase Inhibitors ("Statins"): Atorvastatin (Lipitor) Fluvastatin (Lescol) Lovastatin (Mevacor)

Coenzyme Q10 Blocking of synthesis of mevalonic acid, which is a precursor of

Serum levels of coenzyme Q-10 are reduced but muscle levels are not affected. Therefore, this is probably not clinically

Pravastatin (Pravachol) Rosuvastatin (Crestor) Simvastatin (Zocor)

coenzyme Q10. significant.3367,3370,4404-

10,8915,1209

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

Beta-Carotene Vitamin A Vitamin E Vitamin K

Reduced absorption of fat and fat-soluble vitamins. Reduced plasma lipids may reduce the amount of beta carotene and vitamins A and E carried in the blood.

Reduction in plasma beta-carotene, and vitamin A, E, and K levels is sometimes reported; but levels usually remain within normal limits, even after several years of treatment. Routine supplements are not necessary. Monitor patients closely if they have other risk factors for hypoprothrobinemia or bleeding.4454-8,4460-1,5919,10566-

7,11519

Folic Acid Reduced absorption.

Low folate levels have been reported in children taking large doses of cholestyramine for several months, but the clinical significance is not clear. There are no reports of deficiency in adults. Encourage patients to maintain good dietary intake of folate.4455,4461

Iron Reduced absorption.

Clinically significant iron deficiency has not been reported. If patients need iron supplements for other reasons, advise them to separate doses from bile acid sequestrants by at least 4 hours.9566


Reduced absorption due to binding of intrinsic factor and vitamin B12-intrinsic factor complexes.

Absorption is not completely blocked. Deficiency is unlikely unless the patient has other risk factors for vitamin B12 deficiency.4455,10542-3

Calcium Reduced Osteomalacia has occurred

Vitamin D absorption of vitamin D, which in turn reduces calcium absorption.

rarely in people taking high doses (e.g., >32 g/day cholestyramine) for several years, and having other risk factors for vitamin D deficiency. Such patients may need vitamin D and calcium supplements, but most other patients do not.2672,4458,4460-1,5655,5809,9627

Magnesium Possibly reduced absorption and increased urinary magnesium excretion.

Magnesium deficiency has not been reported. Supplements are not likely to be needed.4096,11548,11587

Phosphate Salts Cholestyramine can bind phosphate in the gut and reduce its absorption.

Cholestyramine doses of 0.2 to 1.1 grams/kg/day in children and 12-16 grams/day in adults have been associated with reduced phosphate levels.4455,5838 Most people taking cholestyramine don't need phosphate supplements unless their dietary intake is low. This interaction can be avoided by separating phosphate and cholestyramine administration by at least 2 hours.

Colestipol can bind phosphate in the gut and reduce its absorption.

In most people taking colestipol, serum phosphate levels remain within normal limits.4460 Most people taking colestipol don't need phosphate supplements unless their dietary intake is low. This interaction can be avoided by separating phosphate and cholestyramine administration by at least 2 hours.

Gemfibrozil (Lopid) Vitamin E Mechanism unknown.

Some studies have reported reduced serum 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)

Calcium Magnesium Potassium

Increased urinary excretion.

Electrolyte disturbances more likely with higher doses. Hypokalemia and hypomagnesemia occur most commonly. May need to use potassium and/or magnesium supplements, or add a potassium-sparing diuretic (which will also spare magnesium).4412,9613-

4,9622

Folic Acid Possibly increased urinary excretion.

Data is very limited, and the need for folic acid supplementation has not been adequately studied.1898

Pyridoxine Increased urinary excretion pyridoxine.

Intravenous furosemide in people with chronic renal failure increases urinary excretion of pyridoxine.8896,9525 However, people with hypertension treated with oral diuretics for several years seem to have normal serum pyridoxine levels.1898 Pyridoxine supplements aren't usually necessary.

Thiamine (B1) Increased thiamine excretion due to increased urinary flow.

Thiamine deficiency may occur in elderly people with poor dietary intake who are on high doses of diuretics (e.g. > 80mg furosemide/day) for several months. Thiamine deficiency may worsen heart failure. A supplement of 200mg/day has improved cardiac function in some, but not all thiamine-

deficient people on diuretics. There are not enough data to recommend routine use of supplements.1283-6,10506-9

Vitamin C Increased urinary losses of vitamin C, probably due to increased water excretion.

Reported in people with chronic renal failure who received a 20 mg intravenous dose of furosemide. Significant vitamin C depletion hasn't been 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)

Magnesium Potassium Zinc

Increased urinary excretion.

Electrolyte disturbances are more likely with higher doses. Hypokalemia and hypomagnesemia occur most commonly. May need to use potassium and/or magnesium supplements, or add a potassium sparing diuretic (which will also spare magnesium).4412,9613-

4,9622

Folic Acid Possibly increased urinary excretion.

Data are very limited, and the need for folic acid supplementation has not been adequately studied.1898

Thiamine (B1) Increased thiamine excretion due to increased urinary flow.

Thiamine deficiency may occur in elderly people with poor dietary intake who are on high doses of diuretics for several months. Thiamine deficiency may worsen heart failure. A supplement of 200 mg/day has improved cardiac function in some thiamine-deficient people on diuretics. There are not enough data to recommend routine supplements.1283-

6,10506-9

Triamterene (Dyrenium) Folic Acid Reduced absorption of folic acid and reduced conversion to the active form.

Megaloblastic anemia is rare unless patients are on chronic therapy and have poor dietary intake or other risk factors for folate deficiency. Monitor folate status in these situation and consider supplements if necessary.4425,4536-7,9375

CENTRAL NERVOUS SYSTEM

ANTICONVULSANTS

Carbamazepine (Atretol, Epitol, Tegretol)

Biotin Competitive inhibition of absorption, increased breakdown, and decreased renal tubular reabsorption.

The clinical significance of this is not known. It is not known if taking biotin supplements is necessary.172,175-6,11698-

700,14501-2


Possibly increased metabolism or decreased synthesis.

It is not known if carnitine supplementation is necessary.1911,12758

Folic Acid Decreased intestinal absorption and induction of hepatic microsomal enzymes leading to increased folic acid metabolism.

Megaloblastic anemia due to folic acid deficiency hasn't been reported with carbamazepine. Low folic acid levels might contribute to mental changes in some people on carbamazepine, but folic acid supplements may worsen seizure control. Advise patients to consult their physician before starting folic acid supplements.4426-9,9359

Calcium Vitamin D

Increases the rate of vitamin D metabolism leading to decreased levels of various forms

Hypocalcemia and osteomalacia have occurred with long-term anticonvulsant therapy. Advise patients taking carbamazepine for 6 months

of vitamin D. Decreased vitamin D levels reduce calcium absorption.

or longer to have their vitamin D and calcium levels checked. Supplements may be needed.2675,10578

Vitamin K Induction of liver enzymes may increase vitamin K metabolism, producing a significant decrease in vitamin K levels in neonates, who haven't built up stores of the vitamin.

Increases risk of neonatal intracranial hemorrhage. Women who need to take carbamazepine during pregnancy should take vitamin K, 10-20 mg/day, during the last month of pregnancy. The baby should receive vitamin K immediately after delivery.10582,11521-5,11533-4

Vitamin E Children taking carbamazepine seem to have lower vitamin E levels compared to children not receiving carbamazepine.

The clinical significance is unknown. It is not known if vitamin E supplements are beneficial.11574-8

Phenytoin (Dilantin), Fosphenytoin (Cerebyx)


The clinical significance of this is not known. It is not known if taking biotin supplements is helpful.175-

6,11698-700,14501

Folic Acid Reduced absorption, increased metabolism, and increased demand for folate as a coenzyme for induced hepatic enzymes.

Folic acid supplements may reduce phenytoin side effects, but can also reduce phenytoin serum levels and may independently worsen seizure control. Advise patients to consult a physician before starting folic acid supplements.4427,4471,4477,4536,

9354-9

Acetyl-L-Carnitine L-carnitine Propionyl-L-Carnitine



Niacin/Niacinamide

Mechanism unknown.

Case reports describe pellagra-like symptoms with phenytoin, but this is rare and supplements are generally not needed.14522-3

Thiamine (B1) Mechanism unknown.

Thiamine deficiency might contribute to neurologic side effects, but there is insufficient evidence to recommend supplements.10510-2


Reduces absorption of vitamin B12.

This may exacerbate the megaloblastic anemia associated with phenytoin, which is primarily caused by folate deficiency. Encourage patients to maintain adequate dietary vitamin B12 intake. Monitor vitamin B12 and folate if symptoms of anemia develop.7843,10502-5

Calcium Vitamin D

Increases the rate of vitamin D metabolism leading to decreased levels of various forms of vitamin D. Phenytoin may also increase the renal excretion of vitamin D metabolites. Decreased vitamin D levels reduce calcium absorption.

Hypocalcemia and osteomalacia have occurred with long-term anticonvulsant therapy. Advise patients taking phenytoin for 6 months or longer that they should have their vitamin D and calcium levels checked. Supplements may be needed.2675,4430-1,4475,10578

Vitamin E Children taking The clinical significance is

phenytoin seem to have lower vitamin E levels compared to children not receiving phenytoin.

unknown. It is not known if vitamin E supplementats are beneficial.11574-8

Vitamin K Induction of liver enzymes may increase vitamin K metabolism, producing a significant decrease in vitamin K levels in neonates who haven't built up stores of the vitamin.

Increased risk of neonatal intracranial hemorrhage. Women who need to take phenytoin during pregnancy should take vitamin K, 10-20 mg/day, during the last month of pregnancy. The baby should receive vitamin K immediately after delivery.10582,11521-5,11533-4

Zinc May chelate zinc and could reduce absorption.

Occasional reports of reduced zinc levels but the clinical significance is unclear and supplements are unlikely to be necessary.11577,11659-

60,11663,11669

Phenobarbital (Luminal, Solfoton) Primidone (Mysoline)


The clinical significance of this is not known. It is not known if taking biotin supplements is helpful.172,175-6,11698-700,14501-2

Folic Acid Reduced absorption, increased metabolism, and increased demand for folate as a coenzyme for induced hepatic enzymes.

Reduced folic acid levels associated with phenobarbital or primidone treatment occasionally lead to megaloblastic anemia, and may contribute to neurological side effects and mental changes. However, folic acid supplements can worsen

seizure control. Advise patients to consult a physician before starting folic acid supplements.4427,4530,4536,9333,

9354-9

Dibecozide Vitamin B12

Reduced absorption

Encourage patients to maintain adequate dietary vitamin B12 intake. Monitor vitamin B12 status if symptoms of anemia develop.7843,10502-5




Vitamin E Children taking phenobarbital seem to have lower vitamin E levels compared to children not receiving phenobarbital.

The clinical significance is unknown. It is not known if vitamin E supplements are beneficial.11574-8

Calcium Vitamin D

Increased rate of vitamin D metabolism leading to decreased levels of various forms of vitamin D and reduced calcium absorption.

Hypocalcemia and osteomalacia can occur with long-term anticonvulsant therapy. Advise patients taking phenobarbital or primidone for 6 months or longer that they should have their vitamin D and calcium levels checked. Supplements may be needed.2675

Vitamin K Induction of liver enzymes may increase vitamin K metabolism, producing a significant decrease in vitamin K levels

Increased risk of neonatal intracranial hemorrhage. Women who need to take these anticonvulsants during pregnancy should take vitamin K, 10-20 mg/day, during the last month of pregnancy. The baby should

in neonates, who haven't built up stores of the vitamin.

receive vitamin K immediately after delivery.10582,11521-5,1533-4

Valproic Acid (Depakene, Depakote)

Folic Acid Mechanism unknown.

Reduced levels occur occasionally, but symptomatic folic acid deficiency has not been reported. Avoid supplements since they may worsen seizure control.4427-

8,9355-6,9359



Valproic acid supplement may not be necessary in patients who have adequate nutrition intake.1911,4528-

9,5798,9612,12758


Mechanism unknown.

There are rare case reports of deficiency, but most people do not need supplements.14505,14523

Zinc May bind with zinc, possibly reducing serum and tissue levels.

Data regarding the effect of valproate on zinc levels are conflicting. Some suggest that lowered zinc levels might contribute to side effects of valproate. Most people are unlikely to need zinc supplements.11652-62

Dopamine agonists

Levodopa (L-DOPA, Larodopa, Dopar)

Potassium Increased urinary potassium losses occur in some people treated with levodopa. The mechanism isn't clear, but the effect doesn't occur when a peripheral decarboxylase inhibitor, such as carbidopa, is

This interaction is unlikely to be significant since most patients get levodopa in combination with carbidopa.7201

used with levodopa (as in Sinemet).

Levodopa / Cabidopa (Sinemet)


Carbidopa may reduce conversion of tryptophan to niacin.

Clinically significant niacin deficiency has not been reported and supplements are unlikely to be necessary.14516

Chlorpromazine (Thorazine) Riboflavin (B2) Interference with conversion to active form, and increased renal excretion.

These effects occur in animals, but there are not enough data to know if this is clinically significant in humans.10515,10518-21

Gastrointestinals

Antacids

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

Calcium Phosphate Salts

Aluminum salts bind phosphate in the gastrointestinal tract. This reduces phosphate levels, which induces movement of calcium from bones into the blood, increasing urinary calcium excretion. High serum magnesium levels can increase urinary calcium excretion.

Prolonged administration of large doses of antacids may lead to hypocalcemia and/or hypophosphatemia. Avoid prolonged administration of large doses, except when used as a phosphate binder in patients with renal failure.2730-1,3371,4400,4623,5979

Chromium Antacids may reduce chromium absorption from the gastrointestinal tract.

Unlikely to be clinically significant.7135

Folic Acid Increased intestinal pH

Long-term use of large doses of antacids can cause

produced by antacids may reduce folic acid absorption.

folate depletion if dietary intake is very low. Most people don't need supplements.2677,8441

Iron Increased gastric pH reduces iron solubility and absorption.

Unlikely to cause iron deficiency. If iron supplements are needed for other conditions, separate dosing times as much as possible. Monitor for adequate response to iron.3046,3072,4539

GI ANTI-INFLAMMATORIES

Sulfasalazine (Azulfidine, Salazopyrin)

Folic Acid Competitive inhibition of folate absorption, and interference with breakdown of dietary folate to its absrobable form. Hemolysis caused by sulfasalazine can increase folate requirements for red blood cell formation.

Decreased folate levels are associated with prolonged sulfasalazine therapy, especially in doses above 2 grams/day. This may lead to megaloblastic anemia, hyperhomocysteinemia, and an increased risk of colon cancer in people with ulcerative colitis. Recommend that patients increase their dietary folate intake 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

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

Calcium Absorption of some calcium supplements, especially the carbonate salt, is decreased by increased gastric pH.

There is not any evidence of a clinically significant effect on calcium levels.2738,4330-

1,5060

Chromium Increased pH may cause formation of less soluble

The clinical significance of this is not known.7135

chromium salts, reducing absorption.

Folic Acid Reduced absorption due to increased pH.

A significant effect on folic acid levels is unlikely unless dietary intake is very low.4483,8441

Iron Reduced iron absorption from the gastrointestinal tract due to reduction in acid.

Reduction in absorption of dietary, non-heme iron occurs, but anemia is unlikely with long-term H2-blocker use in people with normal iron stores. Supplements may be needed in people with other factors contributing to iron deficiency.4483,4539,4540-

1,8876,9578


Decreased gastric acid reduces cleavage of protein-bound dietary vitamin B12, reducing the amount available for absorption.

Deficiency is unlikely unless dietary intake of vitamin B12 is poor, or H2-blockers are taken continuously in high doses for 2 years or more. In these circumstances, monitor for vitamin B12 deficiency and anemia.4539-41,9513-4,9528

Zinc Inhibition of gastric acid secretion might reduce absorption of zinc.

Clinically significant zinc depletion hasn't been reported.11636

LAXATIVES

Mineral Oil Beta-Carotene Calcium Vitamin A Vitamin D Vitamin E Vitamin K

Decreases gastrointestinal absorption.

Occassional use of mineral oil is unlikely to cause deficiency. Advise patients to avoid large doses or regular use of mineral oil.4454,4495-6

Phosphate Salts Mineral oil reduces absorption of

Occasional or short-term use of mineral oil isn't likely to have a clinically

vitamin D, which acts to increase phosphate absorption in the gastrointestinal tract and reabsorption in the kidney tubules.

significant effect on phosphate levels.505,4495

Sodium Phosphates (Fleet Phospho-Soda)

Magnesium Potassium

Increased loss of electrolytes from gastrointestinal tract.

High doses (such as those used for preoperative bowel cleansing) can cause severe electrolyte disturbances. Avoid high doses and monitor electrolyte levels in the elderly and others with risk factors for hypomagnesemia or hypokalemia.8877,9531,9615-6

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

Potassium Increases gastrointestinal losses.

Excessive use of stimulant laxatives may result in hypokalemia. Limit to short-term use of recommended doses. Hypokalemia has been reported in patients undergoing short-term bowel-cleansing regimens. Use with caution in patients who have other risk factors for hypokalemia.4411-2,4425

Calcium Vitamin D

Decreases gastrointestinal absorption.

Prolonged use of high doses of stimulant laxatives can cause hypocalcemia and osteomalacia. Limit to short-term use of recommened doses.11530

PANCREATIC ENZYMES

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

Folic Acid Iron

Reduced absorption due to formation of complexes in the gastrointestinal tract.

Supplements may be needed with prolonged 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 gastric pH may decrease absorption of beta carotene.

Reported with a single dose of a beta-carotene supplement. Whether there is a clinically significant effect on absorption of dietary beta cartene is unknown.31

Calcium Absorption of some calcium supplements, especially the carbonate salt, is decreased by increased gastric pH.

There isn't any evidence of a clinically significant effect on calcium levels.2738,4330-

1,5060

Chromium Increased pH may cause formation of less soluble chromium salts, reducing absorption.


Folic Acid Increased pH could reduce folate absorption.

Use of PPIs for several years does not seem to cause folate deficiency. Supplements are probably not necessary.4483,8441

Iron Reduced iron absorption from the gastrointestinal tract due to lack of acid.

Reduction in absorption of dietary, non-heme iron may occur, but anemia is unlikely with use of PPIs for several years in people with normal iron stores. Supplements may be needed in people with other factors contributing to iron deficiency.4483,4539,8850,9578


Decreased gastric acid reduces cleavage of protein-bound dietary vitamin

Deficiency is unlikely unless dietary intake of vitamin B12 is poor, or PPIs are taken continuously for 2 years or more. It is more

B12, reducing the amount available for absorption.

likely if the patient is rendered achlorhydric. In these circumstances monitor for vitamin B12 deficiency and anemia, and consider supplements if necessary.4483-6,9513,9528

Vitamin C Preliminary data suggests omeprazole reduces vitamin C levels, possibly due to increased destruction of vitamin C at higher gastric pH levels.

It is not known if this is clinically significant.10572

Zinc Each 40 mg vial of pantoprazole IV contains 1 mg EDTA which can chelate zinc.

Pantoprazole IV 240 mg/day for 7 days increases urinary zinc excretion, but serum zinc levels are unchanged.11665 Zinc supplements are not usually necessary with typical doses of pantoprazole IV.

Inhibition of gastric acid secretion might reduce absorption of zinc.

PPIs might reduce absorption of zinc from supplements,11637 but PPIs don't seem to affect zinc absorption from food.11638 Clinically significant zinc depletion has not been reported.

MISCELLANEOUS

Sucralfate Phosphate Salts Sucralfate has phosphate binding properties and reduces phosphate absorption.

Doses of 6-17 grams/day have been used to reduce elevated phosphate levels in patients with renal failure.14594,14595 In people with normal renal function there is a risk of hypophosphatemia if large doses of 6 grams/day or more are used for prolonged

periods.14595 If phosphate supplements and sucralfate are needed concurrently, separate doses by at least 2 hours.

HORMONES

Corticosteroids [Glucocorticoids]: Short-acting Cortisone (Cortone), Hydrocortisone [Cortisol] (Cortef, Hydrocortone) Intermediate-acting Prednisone (Deltasone, Meticorten, Orasone, Panasol-S), Prednisolone (Delta-Cortef, Prelone, Pediapred), Triamcinolone (Aristocort, Atolone, Kenacort), Methylprednisolone (Medrol) Long-acting Dexamethasone (Decadron, Dexameth, Dexone), Betamethasone (Celestone)

Calcium Vitamin D

Increased renal calcium excretion and decreased intestinal calcium absorption. This depletion of calcium creates a greater need for vitamin D, to improve calcium absorption.

Steroid-induced osteoporosis, and the associated increase in fracture risk, are well-recognized consequences of long-term administration of corticosteroids, in doses equivalent to prednisone 7.5 mg/day or higher. Recommend patients maintain a calcium intake of 1500 mg/day and a vitamin D intake of 800 units/day. Monitor levels and consider supplements if necessary.1832,4462-7

Chromium Increases renal excretion of chromium.

Chromium deficiency may contribute to corticosteroid-induced hyperglycemia. The role of chromium supplements has not been adequately studied.5039

Folic Acid Patients with multiple sclerosis treated with methylprednisolone seem to have decreased serum folate levels.


Magnesium Drug-induced bone loss releases magnesium from bone and increases urinary excretion.

Serum magnesium levels are usually not affected and supplements are not necessary.9507-9,9628-9

Potassium Corticosteroids Hypokalemia is dose-

cause sodium retention, resulting in compensatory renal potassium excretion.

dependent and more common with steroids having high mineralocorticoid activity (hydrocortisone, cortisone, fludrocortisone, prednisone, prednisolone). Monitor potassium levels with chronic therapy. If necessary, give supplements, or switch to a steroid with no mineralocorticoid activity (betamethasone, dexamethasone, methylprednisolone, triamcinolone).4425

Strontium Might increase urinary excretion of strontium.


Zinc Shift of zinc from the blood into the tissues and possibly increased loss 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

Folic Acid Possibly reduced absorption, increased excretion, increased protein binding and induction of liver enzymes which use folate.

Folic acid supplements should be considered only in people with a very low dietary intake, or with other conditions which contribute to folate deficiency.4459,4498,7843-4,9371-

3,9532

Magnesium Shift from plasma to tissues.

Monitor magnesium levels in people with other risk factors for hypomagnesemia.9621,9638-40

Pyridoxine (B6) Interference with pyridoxine metabolism.

Reduced plasma pyridoxal phosphate levels have been reported, but may return to normal despite continued therapy, especially with low

doses of estrogen. It's suggested that pyridoxine deficiency contributes to depression, lethargy and fatigue associated with oral contraceptives, but there is no good evidence that supplements help.4459,4498,9504-6,9510

Riboflavin (B2) Possibly reduced absorption or interference with conversion to active form.

Reduced riboflavin levels reported in women with low dietary intake who were taking high-dose oral contraceptives which are no longer available. Riboflavin supplements are not necessary when dietary intake is adequate.4548,9373,9505,10523-

7,10536

Thiamine (B1) Small reduction in activity of the thiamine-dependent enzyme erythrocyte transketolase, suggesting mild thiamine deficiency.

Routine use of thiamine supplements is not necessary.10548,10555

Vitamin A Estrogens stimulate production of retinol binding protein, increasing the amount of vitamin A removed from liver storage and carried in blood.

Vitamin A supplements might help maintain liver stores, but the need for this hasn't been proven.9373,9505,10523,10548


Reduced protein binding, leading to increased

Vitamin B12 supplements are not necessary.4498,4547,7843,9371-

tissue uptake. 3,9505,10123

Vitamin C May reduce absorption, increase breakdown, or increase vitamin C requirements to prevent oxidation of estrogens.

Data are conflicting, but deficiency is unlikely unless dietary vitamin C is very low. Routine supplements are not necessary.10548,10583,10585-

7,11161,11528,11875-6

Zinc Decreases in serum albumin may reduce the amount of zinc carried in the blood. There may also be increased use and uptake of zinc by the tissues due to anabolic effects.

Data are conflicting, but there does not appear to be increased loss of zinc from the body. Supplements are probably not necessary.9505,11642-51

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

Calcium Increased bone turnover may lead to increased urinary calcium losses.

Calcium loss is unlikely to be clinically significant with doses of thyroid hormones used to treat hypothyroidism. Check thyroid function tests to ensure patients are not receiving excessive thyroid hormone doses, which may increase calcium losses.27-

9,2684-5,2695,2697-8,2721

Teriparatide (Forteo) Phosphate Salts Teriparatide increases urinary phosphate excretion and decreases serum phosphate similarly to human parathyroid hormone.

After a single dose of teriparatide, serum phosphate levels fall for about 2 hours and then recover to baseline.14590 This recovery also seems to continue even with several years of treatment, with patients having either no change in serum phosphate levels, or a small decrease which does not take them

below the normal range.14596,14597,14598,14599 Phosphate supplements are not necessary with teriparatide.

RESPIRATORY

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

Magnesium Potassium

Intracellular shift of magnesium and potassium.

May contribute to arrhythmias, especially at high doses and in people with other risk factors. Monitor electrolyte levels during acute use of high doses (e.g., in preterm labor or acute asthma attacks), and in people with other risk factors. With chronic 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

Methylxanthines Theophylline (Slobid, Theo-24, Theo-Dur, Theolair) Aminophylline Oxtriphylline (Choledyl SA) Diphylline (Lufyllin)

Potassium Possibly increased intracellular uptake.

Risk for hypokalemia is dose-dependent. Monitor potassium levels in people on high doses or with other risk factors.9534,9537-9

Pyridoxine (B6) Inhibits conversion of pyridoxine to its active form.

Suggested that pyridoxine deficiency contributes to side effects of theophylline, but data are conflicting. It is not clear whether there is any benefit with pyridoxine supplements.4522,7064,7066,9480,

9503

MISCELLANEOUS

Alcohol Glutathione Alcohol depletes endogenous glutathione.

It is not known if glutathione supplements would be beneficial.

Cobalt Irradiation Dibencozide Vitamin B12

Irradiation of the small bowel can decrease absorption of vitamin B12.

The clinical significance is unknown.15

Cyclosporine (Neoral, Sandimmune)

Magnesium Significant loss of magnesium in the urine, probably due to reduced tubular reabsorption and tubular damage.

Hypomagnesemia may contribute to seizures and neurotoxicity. Monitor serum magnesium levels closely. Supplements may be needed, or dose reduction/discontinuation of cyclosporine.9117,9632-3

Deferoxamine (Desferal) Zinc Dose-dependent increase in urinary zinc elimination.

Some people maintain normal zinc levels due to compensatory mechanisms while 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 chelates zinc, altering zinc absorption.

Doses of disulfiram up to about 320 mg/day may decrease intestinal zinc absorption, while higher doses of 400 mg/day might increase it slightly.11613,11635 The clinical significance of this is not clear.

EDTA Zinc Chelation of metal ions, including zinc, leading to increased urinary excretion.

In the treatment of lead poisoning, calcium disodium EDTA increases urinary zinc excretion 10- to 17-fold, and decreases serum levels 40%. Levels recover after a single course, but repeated courses can cause deficiency. There is concern that supplements may reduce efficacy of EDTA treatment. Use only if clinically necessary.9630,11667-8,11670

Isotretinoin (Accutane, Claravis, Accutane Roche, Isotrex)

Acetyl-L-carnitine L-carnitine Proprionyl-L-

Not known. Reduced carnitine blood levels have been reported, sometimes with symptoms of carnitine deficiency, such

carnitine as myalgia and muscle stiffness.3619 Other studies have found no significant effect of isotretinoin on carnitine blood levels.11557 There is not enough information to recommend routine use of L-carnitine supplements with isotretinoin.

Lanthanum Carbonate Phosphate Salts Lanthanum carbonate binds phosphate in the gut and reduce is absorption.

Lanthanum carbonate is used therapeutically to reduce elevated phosphate levels in patients with renal failure.14588 Avoid lanthanum carbonate in people with normal phosphate levels.

Nitrous oxide (N2O) Dibencozide Vitamin B12

Inactivates the cobalamin form of vitamin B12.

Deficiency symptoms may occur after a single dose of nitrous oxide in people with pre-existing, subclinical deficiency. Check vitamin B12 levels before using nitrous oxide anesthesia in people with risk factors for vitamin B12 deficiency.9527,9532

Orlistat (Xenical) Beta-Carotene Vitamin A Vitamin D Vitamin E Vitamin K

Decreased absorption of fat soluble vitamins from the gastrointestinal tract.

Vitamin levels usually remain within normal limits. The manufacturer of orlistat recommends all patients take a multivitamin supplement, separating the dose from orlistat by a least 2 hours. Monitor clotting times closely in patients taking warfarin and orlistat. 1727,1730,9595,10570-1,11520

Sevelamer Phosphate Salts Sevelamer binds phosphate in the gut by an ion exchange mechanism.

Sevelamer is used to reduce elevated phosphate levels in patients with renal failure. Avoid sevelamer in people with normal phosphate

levels.14588

Sunscreens Vitamin D Frequent and extensive application of sunscreens can reduce vitamin D synthesis in the skin and plasma levels.

Usual use of sunscreen is not likely to cause clinically significant vitamin D deficiency in most people.11507-9

Tacrolimus (FK506, Prograf)

Magnesium Reduced renal tubular reabsorption leads to increased excretion of magnesium.

Hypomagnesemia occurs in a significant proportion of patients. Monitor levels and give supplements as necessary.8900,9620

Documents

Drug Influences Nutrient Levels Depletion