Interactions between your selected drugs and food

Moderate

diazepam food

Applies to: diazepam

GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other
CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The
mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic
enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by
benzodiazepines may be increased in patients who chronically consume large amounts of
alcohol.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered
drugs that are substrates of the CYP450 3A4 isoenzyme. However, the interaction seems to
affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4
(i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits
intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving
grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a
given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse
effects and altered plasma concentrations of drugs that undergo significant presystemic
metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction
is suspected. Orange juice is not expected to interact with these drugs.

References

1. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food

interactions in clinical practice." J Fam Pract 40 (1995): 376-84
2. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E
"Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite
E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
3. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics
of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93

View all 34 references

Moderate

phenytoin food

Applies to: Phenytoin Sodium (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels
when the suspension is given concomitantly with enteral feedings. The mechanism may be
related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or
binding to the tube lumen. Data have been conflicting and some studies have reported no
changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic
consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this
interaction is related to induction of phenytoin metabolism by ethanol during chronic
administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before
and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the
tube with water after administration; however, this method may not entirely avoid the interaction
and is not always clinically feasible. Patients should be closely monitored for clinical and
laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation
of enteral feedings. Dosage adjustments or intravenous administration may be required until
therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be
warned about the interaction between phenytoin and ethanol and they should be advised to notify
their physician if they experience worsening of seizure control or symptoms of toxicity,
including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

1. Cerner Multum, Inc. "Australian Product Information." O 0

2. Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg
Nurs 16 (1984): 289-91
3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

View all 16 references

Moderate

carbamazepine food

Applies to: carbamazepine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of

carbamazepine. Use in combination may result in additive central nervous system depression
and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit

juice (compared to water) increased plasma drug concentrations by approximately 40%. The
proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut
wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit

consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving
carbamazepine therapy should preferably avoid the regular consumption of grapefruits and
grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be
advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or
ataxia) to their physicians.

References

1. Garg SK, Kumar N, Bhargava VK, Prabhakar SK "Effect of grapefruit juice on

carbamazepine bioavailability in patients with epilepsy." Clin Pharmacol Ther 64 (1998):
286-8
2. "Product Information. Tegretol (carbamazepine)." Basel Pharmaceuticals, Summit, NJ.
3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-
felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin
Pharmacol Ther 68 (2000): 468-77

Interactions between your selected drugs and food

Moderate

sucralfate food

Applies to: sucralfate

When sucralfate is given with enteral (tube) feedings, the feeding tube may become clogged
and/or sucralfate may not work as well. You could interrupt the feeding for 1 hour before and
after the sucralfate dose. However, this still may not entirely avoid the interaction and may not
always be feasible. It is important to tell your doctor about all other medications you use,
including vitamins and herbs. Do not stop using any medications without first talking to your
doctor.

Moderate

isoniazid food

Applies to: isoniazid, isoniazid / pyrazinamide / rifampin

Food decreases the levels of isoniazid in your body. Take isoniazid on an empty stomach at least
1 hour before or 2 hours after a meal. This will make it easier for your body to absorb the
medication. If nausea occurs, ask your doctor if you can take isoniazid with food. Avoid alcohol
while taking isoniazid. Alcohol may increase the risk of damage to the liver during isoniazid
treatment. Alcohol can also cause isoniazid side effects to get worse. Contact your doctor if you
experience flushing, chills, headache, nausea, vomiting, and diarrhea.
Moderate

budesonide food

Applies to: Symbicort (budesonide / formoterol)

You should avoid the regular consumption of large amounts of grapefruits and grapefruit juice
while taking budesonide. Grapefruit can raise the levels of budesonide in your body and lead to
increased side effects. Do not increase or decrease the amount of grapefruit products in your diet
without first talking to your doctor.

Interactions between your selected drugs and food

Major

simvastatin food

Applies to: simvastatin

GENERALLY AVOID: Coadministration with grapefruit juice may significantly increase the
plasma concentrations of lovastatin and simvastatin and their active acid metabolites. The
proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut
wall by certain compounds present in grapefruit. When a single 60 mg dose of simvastatin was
coadministered with 200 mL of double-strength grapefruit juice three times a day, simvastatin
systemic exposure (AUC) increased by 16-fold and simvastatin acid AUC increased by 7-fold.
Administration of a single 20 mg dose of simvastatin with 8 ounces of single-strength grapefruit
juice increased the AUC of simvastatin and simvastatin acid by 1.9-fold and 1.3-fold,
respectively. The interaction has also been reported with lovastatin, which has a similar
metabolic profile to simvastatin. Clinically, high levels of HMG-CoA reductase inhibitory
activity in plasma is associated with an increased risk of musculoskeletal toxicity. Myopathy
manifested as muscle pain and/or weakness associated with grossly elevated creatine kinase
exceeding ten times the upper limit of normal has been reported occasionally. Rhabdomyolysis
has also occurred rarely, which may be accompanied by acute renal failure secondary to
myoglobinuria and may result in death.

ADJUST DOSING INTERVAL: Fibres such as oat bran and pectin may diminish the
pharmacologic effects of HMG-CoA reductase inhibitors by interfering with their absorption
from the gastrointestinal tract.

MANAGEMENT: Patients receiving therapy with lovastatin, simvastatin, or red yeast rice
(which contains lovastatin) should be advised to avoid the consumption of grapefruit and
grapefruit juice. Fluvastatin, pravastatin, pitavastatin, and rosuvastatin are metabolized by other
enzymes and may be preferable alternatives in some individuals. All patients receiving statin
therapy should be advised to promptly report any unexplained muscle pain, tenderness or
weakness, particularly if accompanied by fever, malaise and/or dark colored urine. Therapy
should be discontinued if creatine kinase is markedly elevated in the absence of strenuous
exercise or if myopathy is otherwise suspected or diagnosed. Also, patients should either refrain
from the use of oat bran and pectin or, if concurrent use cannot be avoided, to separate the
administration times by at least 2 to 4 hours.

References

1. Richter WO, Jacob BG, Schwandt P "Interaction between fibre and lovastatin." Lancet
338 (1991): 706
2. Neuvonen PJ, Backman JT, Niemi M "Pharmacokinetic comparison of the potential over-
the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin." Clin
Pharmacokinet 47 (2008): 463-74
3. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice-simvastatin interaction: Effect on
serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase
inhibitors." Clin Pharmacol Ther 64 (1998): 477-83

View all 8 references

Moderate

valsartan food

Applies to: valsartan

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt

substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II
receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-
induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal
insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use
potassium-containing salt substitutes or over-the-counter potassium supplements without
consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum
potassium levels is recommended. Patients should also be advised to seek medical attention if
they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion,
tingling of the extremities, or feelings of heaviness in the legs.

References

1. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals, East Hanover, NJ.

2. "Product Information. Cozaar (losartan)." Merck & Co, Inc, West Point, PA.

Moderate

nicardipine food
Applies to: nicardipine

GENERALLY AVOID: The consumption of grapefruit juice may be associated with

significantly increased plasma concentrations of some calcium channel blockers (CCBs) when
they are administered orally. The mechanism is inhibition of CYP450 3A4-mediated first-pass
metabolism in the gut wall by certain compounds present in grapefruits. This interaction has
been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude)
felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual
variability. Grapefruit juice resulted in more than twofold increases in felodipine, nifedipine, and
nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding

grapefruit juice. Patients treated orally with other calcium channel blockers should be advised to
avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue
fluctuations in serum drug levels. Increased effects on blood pressure may persist for up to 4
days after the consumption of grapefruit juice. Monitoring for calcium channel blocker adverse
effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

References

1. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
2. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine
interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin
Pharmacol Ther 64 (1998): 248-56
3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the
interaction." Clin Pharmacokinet 26 (1994): 91-8

View all 18 references

Moderate

irbesartan food

Applies to: irbesartan

GENERALLY AVOID: Moderate-to-high dietary intake of potassium, especially salt

substitutes, may increase the risk of hyperkalemia in some patients who are using angiotensin II
receptor blockers (ARBs). ARBs can promote hyperkalemia through inhibition of angiotensin II-
induced aldosterone secretion. Patients with diabetes, heart failure, dehydration, or renal
insufficiency have a greater risk of developing hyperkalemia.

MANAGEMENT: Patients should receive dietary counseling and be advised to not use
potassium-containing salt substitutes or over-the-counter potassium supplements without
consulting their physician. If salt substitutes are used concurrently, regular monitoring of serum
potassium levels is recommended. Patients should also be advised to seek medical attention if
they experience symptoms of hyperkalemia such as weakness, irregular heartbeat, confusion,
tingling of the extremities, or feelings of heaviness in the legs.
References

1. "Product Information. Diovan (valsartan)." Novartis Pharmaceuticals, East Hanover, NJ.

2. "Product Information. Cozaar (losartan)." Merck & Co, Inc, West Point, PA.

Minor

amlodipine food

Applies to: amlodipine

The consumption of grapefruit juice may slightly increase plasma concentrations of amlodipine.
The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by
certain compounds present in grapefruits. Data have been conflicting and the clinical
significance is unknown. Monitoring for calcium channel blocker adverse effects (e.g., headache,
hypotension, syncope, tachycardia, edema) is recommended.

References

1. Kane GC, Lipsky JJ "Drug-grapefruit juice interactions." Mayo Clin Proc 75 (2000): 933-
42
2. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics
of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
3. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the
interaction." Clin Pharmacokinet 26 (1994): 91-8

View all 6 references

Minor

digoxin food

Applies to: digoxin

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability
by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be
advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is
being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is
increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain
compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice
with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5
mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by
just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism
does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the
interaction is unlikely to be of clinical significance.
References

1. Darcy PF "Nutrient-drug interactions." Adverse Drug React Toxicol Rev 14 (1995): 233-
54
2. Becquemont L, Verstuyft C, Kerb R, et al. "Effect of grapefruit juice on digoxin
pharmacokinetics in humans." Clin Pharmacol Ther 70 (2001): 311-6

Interactions between your selected drugs and food

Moderate

chlorpheniramine food

Applies to: chlorpheniramine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-
active agents. Use in combination may result in additive central nervous system depression
and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and
advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to
avoid hazardous activities requiring complete mental alertness and motor coordination until they
know how these agents affect them, and to notify their physician if they experience excessive or
prolonged CNS effects that interfere with their normal activities.

References

1. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol
and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7
2. Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the
Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc.
(1990):
3. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.

View all 4 references

Moderate

diazepam food

Applies to: diazepam

GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other
CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The
mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic
enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by
benzodiazepines may be increased in patients who chronically consume large amounts of
alcohol.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered
drugs that are substrates of the CYP450 3A4 isoenzyme. However, the interaction seems to
affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4
(i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits
intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving
grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a
given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse
effects and altered plasma concentrations of drugs that undergo significant presystemic
metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction
is suspected. Orange juice is not expected to interact with these drugs.

References

1. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food

interactions in clinical practice." J Fam Pract 40 (1995): 376-84
2. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E
"Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite
E3174 in healthy volunteers." Ther Drug Monit 23 (2001): 369-73
3. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics
of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93

View all 34 references

Moderate

phenytoin food

Applies to: Phenytoin Sodium (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels

when the suspension is given concomitantly with enteral feedings. The mechanism may be
related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or
binding to the tube lumen. Data have been conflicting and some studies have reported no
changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic
consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this
interaction is related to induction of phenytoin metabolism by ethanol during chronic
administration. Other hydantoin derivatives may be similarly affected by ethanol.
MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before
and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the
tube with water after administration; however, this method may not entirely avoid the interaction
and is not always clinically feasible. Patients should be closely monitored for clinical and
laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation
of enteral feedings. Dosage adjustments or intravenous administration may be required until
therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be
warned about the interaction between phenytoin and ethanol and they should be advised to notify
their physician if they experience worsening of seizure control or symptoms of toxicity,
including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

1. Cerner Multum, Inc. "Australian Product Information." O 0

2. Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg
Nurs 16 (1984): 289-91
3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0