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, Mefenamic
Acid (Ponstel), Meloxicam
(Mobic), Nabumetone
(Relafen), Naproxen (Anaprox,
Naprosyn, Naprelan),
Oxaprozin (Daypro), Piroxicam
(Feldene), Sulindac
(Clinoril), Tolmetin
(Tolectin) |
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. |
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
unknown. |
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 reduce AIDS-related
opportunistic infections, but have also been
linked to increased
mortality.6565-6 |
Acetyl-L-carnitine
L-carnitine
Proprionyl-L-carnitine |
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 |
Niacin and Niacinamide |
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 |
Niacin and Niacinamide |
Isoniazid inhibits the
conversion of tryptophan to niacin. It also
has structural similarities to niacinamide
and may interfere with its activity. |
Might induce pellagra if taken
for long periods, particularly in poorly
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) |
Acetyl-L-carnitine
L-carnitine
Proprionyl-L-carnitine |
Increased urinary excretion of
L-carnitine. |
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 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 |
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. |
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 |
Cytosine Arabinoside
(Cytosar-U) |
Vitamin E |
High doses of chemotherapy
seems to reduce levels of vitamin E. |
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
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 |
Etoposide (Etopophos,
VePesid, Toposar) |
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 |
Ifosamide (Ifex) |
Acetyl-L-carnitine
L-carnitine
Proprionyl-L-carnitine |
Increased urinary excretion of
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. |
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 |
Mercaptopurine (6-MP,
Purinethol) |
Niacin and Niacinamide |
Interferes with conversion of
niacin to nicotinamide adenine dinucleotide
(NAD), due to structural similarities to
adenine. |
May cause pellagra if high
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
Vitamin B12 |
Malabsorption of dietary
vitamin B12 and possibly folic acid. |
The Glucophage package
insert recommends 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 |
Dibencozide
Vitamin B12 |
Disruption of intestinal
mucosal function by colchicine can reduce
absorption. |
Colchicine 1-2 mg/day doesn't
affect vitamin B12 serum levels, but higher
doses may. Monitor vitamin B12 levels in
people taking 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)
Pravastatin (Pravachol)
Rosuvastatin (Crestor)
Simvastatin (Zocor) |
Coenzyme Q10 |
Blocking of synthesis of
mevalonic acid, which is a precursor of
coenzyme Q10. |
Serum levels of coenzyme Q-10
are reduced but muscle levels are not
affected. Therefore, this is probably not
clinically
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 |
Dibencozide
Vitamin B12 |
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
Vitamin D |
Reduced absorption of vitamin
D, which in turn reduces calcium
absorption. |
Osteomalacia has occurred
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 |
Acetyl-L-Carnitine
L-Carnitine
Propionyl-L-Carnitine |
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 of vitamin D. Decreased
vitamin D levels reduce calcium
absorption. |
Hypocalcemia and osteomalacia
have occurred with long-term anticonvulsant
therapy. Advise patients taking
carbamazepine for 6 months 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) |
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
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 |
Possibly increased metabolism
or decreased synthesis. |
It is not known if carnitine
supplementation is
necessary.1911,12758 |
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 |
Dibencozide
Vitamin B12 |
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 phenytoin seem
to have lower vitamin E levels compared to
children not receiving phenytoin. |
The clinical significance is
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) |
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
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 |
Acetyl-L-Carnitine
L-Carnitine
Propionyl-L-Carnitine |
Possibly increased metabolism
or decreased synthesis. |
It is not known if carnitine
supplementation is
necessary.1911,12758 |
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 in
neonates, who haven't built up stores of
the vitamin. |
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 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 |
Acetyl-L-Carnitine
L-Carnitine
Propionyl-L-Carnitine |
Possibly increased metabolism
or decreased synthesis. |
Valproic acid supplement may
not be necessary in patients who have
adequate nutrition
intake.1911,4528-9,5798,9612,12758 |
Niacin and Niacinamide |
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 used with levodopa (as in
Sinemet). |
This interaction is unlikely
to be significant since most patients get
levodopa in combination with
carbidopa.7201 |
Levodopa / Cabidopa
(Sinemet) |
Niacin and Niacinamide |
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
produced by antacids may reduce folic acid
absorption. |
Long-term use of large doses
of antacids can cause 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 chromium salts,
reducing absorption. |
The clinical significance of
this is not known.7135 |
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 |
Dibencozide
Vitamin B12 |
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 vitamin D, which acts to increase
phosphate absorption in the
gastrointestinal tract and reabsorption in
the kidney tubules. |
Occasional or short-term use
of mineral oil isn't likely to have a
clinically 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. |
The clinical significance of
this is not known.7135 |
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 |
Dibencozide
Vitamin B12 |
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
PPIs are taken continuously for 2 years or
more. It is more 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. |
The clinical significance of
this is not known.9362 |
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 cause sodium
retention, resulting in compensatory renal
potassium excretion. |
Hypokalemia is dose-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. |
The clinical significance of
this is not known.11405 |
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 |
Dibencozide
Vitamin B12 |
Reduced protein binding,
leading to increased tissue uptake. |
Vitamin B12 supplements are
not
necessary.4498,4547,7843,9371-3,9505,10123 |
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-carnitine |
Not known. |
Reduced carnitine blood levels
have been reported, sometimes with symptoms
of carnitine deficiency, such 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 |
Footnote: Oral L-carnitine
supplementation is strongly suggested for
the following groups: patients with certain
secondary carnitine deficiency syndromes;
symptomatic VPA-associated hyperammonemia;
multiple risk 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. |