Resep 1 (Rica)

Monitor Closely

 diclofenac + mefenamic acid

diclofenac and mefenamic acid both increase anticoagulation. Use Caution/Monitor.

 diclofenac + mefenamic acid

diclofenac and mefenamic acid both increase serum potassium. Use Caution/Monitor.

Minor

 diclofenac + mefenamic acid

diclofenac will increase the level or effect of mefenamic acid by acidic (anionic) drug
competition for renal tubular clearance. Minor/Significance Unknown.

Resep 1 Ari

Monitor Closely

 aspirin + bisoprolol

aspirin decreases effects of bisoprolol by pharmacodynamic antagonism. Use

Caution/Monitor. Long term (>1 wk) NSAID use. NSAIDs decrease prostaglandin
synthesis.

 bisoprolol + amlodipine

bisoprolol and amlodipine both increase anti-hypertensive channel blocking. Modify

Therapy/Monitor Closely.

 bisoprolol + aspirin

bisoprolol and aspirin both increase serum potassium. Use Caution/Monitor.

 bisoprolol + hydrochlorothiazide

bisoprolol increases and hydrochlorothiazide decreases serum potassium. Effect of

interaction is not clear, use caution. Use Caution/Monitor.

 aspirin + hydrochlorothiazide
 aspirin increases and hydrochlorothiazide decreases serum potassium. Effect of
interaction is not clear, use caution. Use Caution/Monitor.

Minor

 hydrochlorothiazide + aspirin

hydrochlorothiazide will increase the level or effect of aspirin by acidic (anionic) drug
competition for renal tubular clearance. Minor/Significance Unknown.

Resep 2 Ari

Monitor Closely

 aspirin + clopidogrel

aspirin, clopidogrel. Either increases toxicity of the other by pharmacodynamic

synergism. Use Caution/Monitor. The need for simultaneous use of low-dose aspirin and
anticoagulant or antiplatelet agents are common for patients with cardiovascular disease;
monitor closely.

Minor

 aspirin + cyanocobalamin

aspirin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only

to oral form of both agents. Minor/Significance Unknown.

 ranitidine + cyanocobalamin

ranitidine decreases levels of cyanocobalamin by inhibition of GI absorption. Applies

only to oral form of both agents. Minor/Significance Unknown.

Interactions between your drugs

Moderate

aspirin amlodipine

Applies to: aspirin, amlodipine

Before using aspirin, tell your doctor if you also use amLODIPine. The combination may cause
your blood pressure to increase. You may need a dose adjustment or your blood pressure
checked more often. Also, if you are already taking the combination and stop taking aspirin, your
blood pressure may decrease. 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.

MONITOR: Limited data indicate that some cyclooxygenase inhibitors may attenuate the
antihypertensive effects of some calcium channel blockers. The mechanism appears to be related
to an alteration of vascular tone, which is dependent on prostacyclins and other vasodilatory
prostanoids. When a nonsteroidal anti-inflammatory drug (NSAID) is added to the regimen of a
patient who is already taking a calcium channel blocker, increased blood pressure may result.
Also, the clinician should be aware that the risk of hypotension is increased when NSAIDs are
withdrawn from the regimen.

MANAGEMENT: Monitoring for altered blood pressure control is recommended.

References

1. Cremer KF, Pieper JA, Joyal M, Mehta J "Effects of diltiazem, dipyridamole, and their
combination on hemostasis." Clin Pharmacol Ther 36 (1984): 641-4
2. Deleeuw PW "Nonsteroidal anti-inflammatory drugs and hypertension: the risks in perspective."
Drugs 51 (1996): 179-87
3. "Product Information. Arthrotec (diclofenac-misoprostol)." Searle, Skokie, IL.
4. Ring ME, Corrigan JJ, Fenster PE "Effects of oral diltiazem on platelet function: alone and in
combination with "low dose" aspirin." Thromb Res 44 (1986): 391-400
5. "Product Information. Duract (bromfenac)." Wyeth-Ayerst Laboratories, Philadelphia, PA.
6. Houston MC, Weir M, Gray J, et al "The effects of nonsteroidal anti-inflammatory drugs on blood
pressures of patients with hypertension controlled by verapamil." Arch Intern Med 155 (1995):
1049-54
7. Zanchetti A, Hansson L, Leonetti G, et al. "Low-dose aspirin does not interfere with the blood
pressure-lowering effects of antihypertensive therapy." J Hypertens 20 (2002): 1015-1022
8. Altman R, Scazziota A, Dujovne C "Diltiazem potentiates the inhibitory effect of aspirin on
platelet aggregation." Clin Pharmacol Ther 44 (1988): 320-5
9. Minuz P, Pancera P, Ribul M, et al "Amlodipine and haemodynamic effects of cyclo-oxygenase
inhibition." Br J Clin Pharmacol 39 (1995): 45-50

Switch to consumer interaction data

Moderate/mayor 1 established

aspirin clopidogrel

Applies to: aspirin, clopidogrel

Before using aspirin, tell your doctor if you also use clopidogrel. This combination may cause
unusual bleeding, severe abdominal pain, weakness, and the appearance of black, tarry stools. If
you take both medications together, tell your doctor if you have any of these symptoms. You
may need a dose adjustment if you take both medications. You should also avoid any other over-
the-counter NSAID products. 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.

MONITOR: Clopidogrel has been shown to potentiate the inhibition of platelet aggregation due
to aspirin. Single-dose studies have not shown a prolongation of bleeding time when aspirin was
added to clopidogrel; however, the risk of gastrointestinal (GI) bleeding may be increased. A
large clinical trial reported that clopidogrel 75 mg/day plus aspirin 75 to 325 mg/day for up to 1
year was associated with a higher incidence of major GI bleeding (1.3% vs 0.7% with aspirin
alone). These two medications are routinely used together for their additive antiplatelet,
antistroke effect. The safety of chronic administration of aspirin or other salicylates with
clopidogrel has not been established.

MANAGEMENT: Until further data are available, caution is recommended, especially in

patients at risk of bleeding (i.e., GI ulceration), if clopidogrel is coadministered on a long-term
basis with drugs that may cause GI lesions. Patients should be advised to promptly report any
signs of bleeding to their physician, including pain, red or black stools, or bloody or coffee-
ground emesis. Patients should also be counseled to avoid any other over-the-counter salicylate
products.

References

1. Klinkhardt U, Kirchmaier CM, Westrup D, Graff J, Mahnel R, Breddin HK, Harder S "Ex vivo-in
vitro interaction between aspirin, clopidogrel, and the glycoprotein IIb/IIIa inhibitors abciximab
and SR121566A." Clin Pharmacol Ther 67 (2000): 305-13
2. "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb, Princeton, NJ.

Switch to consumer interaction data

Moderate/mayor 1 suspected

atorvastatin clopidogrel

Applies to: atorvastatin, clopidogrel

Talk to your doctor before using atorvastatin and clopidogrel. This combination may reduce the
effects of clopidogrel. Call your doctor promptly if you have any signs of blood clots such as
chest pain, shortness of breath, sudden loss of vision, or pain, redness or swelling in an
extremity. You may need a dose adjustment or special test if you take both medications. It is
important that you tell your healthcare provider about all other medications that you are using
including vitamins and herbs. Do not stop using your medications without talking to your doctor
first.
MONITOR: The concomitant administration of atorvastatin may reduce the metabolic activation
of the prodrug clopidogrel and its antiplatelet effects. The proposed mechanism is competitive
inhibition of CYP450 3A4 enzymatic activity, which is responsible for the conversion of
clopidogrel to its active metabolite. However, data have been conflicting. In a trial with coronary
stent implant patients receiving clopidogrel 75 mg/day (n=44), the percent platelet aggregation
was 34% with no atorvastatin, 58% with atorvastatin 10 mg, 74% with 20 mg, and 89% with 40
mg. Results from an in vitro study suggest that equimolar concentrations of atorvastatin inhibit
clopidogrel metabolism by more than 90 %. However, in a post hoc analysis of a trial with
percutaneous coronary intervention patients, no statistical differences in the incidence of
bleeding, stroke, myocardial infarction, or death were found at 1 year with concomitant
administration of clopidogrel 75 mg/day and CYP450 3A4-metabolized HMG-CoA reductase
inhibitors (n=1001, atorvastatin, lovastatin, simvastatin, cerivastatin) or other statins (n=158,
pravastatin, fluvastatin).

MANAGEMENT: Until more information is available, monitoring for altered efficacy of

clopidogrel may be advisable if atorvastatin is coadministered with clopidogrel. Pravastatin,
fluvastatin, and rosuvastatin are not metabolized by CYP450 3A4 and are theoretically not
expected to interact with clopidogrel.

References

1. Clarke TA, Waskell LA "The metabolism of clopidogrel is catalyzed by human cytochrome P450
3A and is inhibited by atorvastatin." Drug Metab Dispos 31 (2003): 53-9
2. Damkier P "Atorvastatin and clopidogrel." Circulation 108 (2003): e96; author reply e96
3. Lau WC, Waskell LA, Watkins PB, et al. "Atorvastatin reduces the ability of clopidogrel to inhibit
platelet aggregation: a new drug-drug interaction." Circulation 107 (2003): 32-7
4. Serebruany VL, Steinhubl SR, Hennekens CH "Are antiplatelet effects of clopidogrel inhibited by
atorvastatin? A research question formulated but not yet adequately tested." Circulation 107
(2003): 1568-9
5. Saw J, Steinhubl SR, Berger PB, et al. "Lack of Adverse Clopidogrel-Atorvastatin Clinical
Interaction From Secondary Analysis of a Randomized, Placebo-Controlled Clopidogrel Trial."
Circulation 108 (2003): 921-924
6. Shechter M "Atorvastatin and the ability of clopidogrel to inhibit platelet aggregation."
Circulation 107 (2003): e210; author reply e210
7. Neubauer H, Gunesdogan B, Hanefeld C, Spiecker M, Mugge A "Lipophilic statins interfere with
the inhibitory effects of clopidogrel on platelet function - a flow cytometry study." Eur Heart J 24
(2003): 1744-1749

Switch to consumer interaction data

Minor

ranitidine cyanocobalamin

Applies to: ranitidine, cyanocobalamin

Consumer information for this minor interaction is not currently available. Some minor drug interactions
may not be clinically relevant in all patients. Minor drug interactions do not usually cause harm or
require a change in therapy. However, your healthcare provider can determine if adjustments to your
medications are needed.

By reducing or suppressing gastric acid secretion, H2-receptor antagonists and proton pump
inhibitors may interfere with the gastrointestinal absorption of vitamin B12, a process that is
dependent on the presence of gastric acid and pepsin. Clinical studies have shown that dietary
(i.e., protein-bound) vitamin B12 malabsorption can occur during treatment with these agents,
particularly proton pump inhibitors, although the likelihood of developing clinically significant
deficiency over time is unknown. There has been one reported case of vitamin B12 deficiency
with megaloblastic anemia in a patient who received omeprazole at a minimum of 40 mg/day for
4 years. Also uncertain is whether acid reduction or suppression can affect the absorption of
vitamin B12 ingested in the form of oral supplements such as cyanocobalamin. Non-oral routes
of administration (e.g., parenteral, intranasal, sublingual) are generally preferred in the treatment
of B12 deficiency-related anemia.

References

1. Lavy NW "Omeprazole and vitamin B12." Ann Intern Med 121 (1994): 74
2. Salom IL, Silvis SE, Doscherholmen A "Effect of cimetidine on the absorption of vitamin B12."
Scand J Gastroenterol 17 (1982): 129-31
3. Bradford GS, Taylor CT "Omeprazole and vitamin B-12 deficiency." Ann Pharmacother 33 (1999):
641-3
4. Dutta SK "Vitamin b-12 malabsorption and omeprazole therapy." J Am Coll Nutr 13 (1994): 544-5
5. Marcuard SP, Albernaz L, Khazanie PG "Omeprazole therapy causes malabsorption of
cyanocobalamin (vitamin-b12)." Ann Intern Med 120 (1994): 211-5

Drug and food interactions

Moderate

atorvastatin food

Applies to: atorvastatin

Grapefruit juice can increase the blood levels of atorvastatin. This can increase the risk of side
effects such as liver damage and a rare but serious condition called rhabdomyolysis that involves
the breakdown of skeletal muscle tissue. In some cases, rhabdomyolysis can cause kidney
damage and even death. You should limit your consumption of grapefruit juice to no more than 1
quart per day during treatment with atorvastatin. Let your doctor know immediately if you have
unexplained muscle pain, tenderness, or weakness during treatment, especially if these symptoms
are accompanied by fever or dark colored urine. You should also seek immediate medical
attention if you develop fever, chills, joint pain or swelling, unusual bleeding or bruising, skin
rash, itching, loss of appetite, fatigue, nausea, vomiting, dark colored urine, and/or yellowing of
the skin or eyes, as these may be signs and symptoms of liver damage. 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.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma
concentrations of atorvastatin. 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
40 mg dose of atorvastatin was coadministered with 240 mL of grapefruit juice, atorvastatin peak
plasma concentration (Cmax) and systemic exposure (AUC) increased by 16% and 37%,
respectively. Greater increases in Cmax (up to 71%) and/or AUC (up to 2.5 fold) have been
reported with excessive consumption of grapefruit juice (>=750 mL to 1.2 liters per day).
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 atorvastatin should limit their consumption of
grapefruit juice to no more than 1 liter per day. Patients 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.
In addition, 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. Lilja JJ, Kivisto KT, Neuvonen PJ "Grapefruit juice increases serum concentrations of atorvastatin
and has no effect on pravastatin." Clin Pharmacol Ther 66 (1999): 118-27
3. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, Radtke M "Metabolism
of cerivastatin by human liver microsomes in vitro. Characterization of primary metabolic
pathways and of cytochrome P45 isozymes involved." Drug Metab Dispos 25 (1997): 321-31
4. "Product Information. Lipitor (atorvastatin)." Parke-Davis, Morris Plains, NJ.
5. McMillan K "Considerations in the formulary selection of hydroxymethylglutaryl coenzyme a
reductase inhibitors." Am J Health Syst Pharm 53 (1996): 2206-14
6. 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
7. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin
Pharmacol 46 (1998): 101-10
Minor

amlodipine food

Applies to: amlodipine

Consumer information for this minor interaction is not currently available. Some minor drug interactions
may not be clinically relevant in all patients. Minor drug interactions do not usually cause harm or
require a change in therapy. However, your healthcare provider can determine if adjustments to your
medications are needed.

Interactions between your drugs

Moderate

hydrochlorothiazide omeprazole

Applies to: hydrochlorothiazide, omeprazole

Using omeprazole together with hydroCHLOROthiazide may cause a condition called

hypomagnesemia, or low blood magnesium. Drugs known as proton pump inhibitors including
omeprazole can cause hypomagnesemia when used for a prolonged period, and the risk may be
further increased when combined with other medications that also have this effect such as
hydroCHLOROthiazide. In severe cases, hypomagnesemia can lead to irregular heart rhythm,
palpitations, muscle spasm, tremor, or seizures. In children, abnormal heart rhythm may cause
fatigue, upset stomach, dizziness, and lightheadedness. A dose adjustment or more frequent
monitoring by the doctor may be required to safely use both medications. If you are using an
over-the-counter proton pump inhibitor medication such as Prilosec OTC, Zegerid OTC or
Prevacid 24 HR, you should follow the directions on the package carefully. Do not use the
medication more frequently or for a longer period than recommended on the label unless
otherwise prescribed by your doctor. 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.

MONITOR: Chronic use of proton pump inhibitors (PPIs) may induce hypomagnesemia, and the
risk may be increased during concomitant use of diuretics or other agents that can cause
magnesium loss. The mechanism via which hypomagnesemia may occur during long-term PPI
use is unknown, although changes in intestinal absorption of magnesium may be involved.
Hypomagnesemia has been reported rarely in patients treated with PPIs for at least three months,
but in most cases, after a year or more. Serious adverse events include tetany, seizures, tremor,
carpopedal spasm, atrial fibrillation, supraventricular tachycardia, and abnormal QT interval;
however, patients do not always exhibit these symptoms. Hypomagnesemia can also cause
impaired parathyroid hormone secretion, which may lead to hypocalcemia. In approximately
25% of the cases of PPI-associated hypomagnesemia reviewed by the FDA, the condition did not
resolve with magnesium supplementation alone but also required discontinuation of the PPI.
Both positive dechallenge as well as positive rechallenge (i.e., resolution of hypomagnesemia
with PPI cessation and recurrence with PPI resumption) were reported in some cases. After
discontinuing the PPI, the median time required for magnesium levels to normalize was one
week. After restarting the PPI, the median time for hypomagnesemia to recur was two weeks.

MANAGEMENT: Monitoring of serum magnesium levels is recommended prior to initiation of

therapy and periodically thereafter if prolonged treatment with a proton pump inhibitor is
anticipated or when combined with other agents that can cause hypomagnesemia such as
diuretics, aminoglycosides, cation exchange resins, amphotericin B, cetuximab, cisplatin,
cyclosporine, foscarnet, panitumumab, pentamidine, and tacrolimus. Patients should be advised
to seek immediate medical attention if they develop potential signs and symptoms of
hypomagnesemia such as palpitations, arrhythmia, muscle spasm, tremor, or convulsions. In
children, abnormal heart rates may cause fatigue, upset stomach, dizziness, and lightheadedness.
Magnesium replacement as well as discontinuation of the PPI may be required in some patients.

References

1. FDA. U.S. Food and Drug Administration "FDA Drug Safety Communication: Low magnesium
levels can be associated with long-term use of proton pump inhibitor drugs (PPIs). Available
from: URL: http://www.fda.gov/Drugs/DrugSafety/ucm245011.htm." ([2011 Mar 2]):

Switch to consumer interaction data

Moderate

aspirin amlodipine

Applies to: aspirin, amlodipine

Before using aspirin, tell your doctor if you also use amLODIPine. The combination may cause
your blood pressure to increase. You may need a dose adjustment or your blood pressure
checked more often. Also, if you are already taking the combination and stop taking aspirin, your
blood pressure may decrease. 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.

MONITOR: Limited data indicate that some cyclooxygenase inhibitors may attenuate the
antihypertensive effects of some calcium channel blockers. The mechanism appears to be related
to an alteration of vascular tone, which is dependent on prostacyclins and other vasodilatory
prostanoids. When a nonsteroidal anti-inflammatory drug (NSAID) is added to the regimen of a
patient who is already taking a calcium channel blocker, increased blood pressure may result.
Also, the clinician should be aware that the risk of hypotension is increased when NSAIDs are
withdrawn from the regimen.

MANAGEMENT: Monitoring for altered blood pressure control is recommended.

References

1. Cremer KF, Pieper JA, Joyal M, Mehta J "Effects of diltiazem, dipyridamole, and their
combination on hemostasis." Clin Pharmacol Ther 36 (1984): 641-4
2. Deleeuw PW "Nonsteroidal anti-inflammatory drugs and hypertension: the risks in perspective."
Drugs 51 (1996): 179-87
3. "Product Information. Arthrotec (diclofenac-misoprostol)." Searle, Skokie, IL.

View all 9 references

Switch to consumer interaction data

Moderate

hydrochlorothiazide bisoprolol

Applies to: hydrochlorothiazide, bisoprolol

Using hydroCHLOROthiazide and bisoprolol together may lower your blood pressure and slow
your heart rate. This can cause dizziness, or feeling like you might pass out, weakness, fainting,
fast or irregular heartbeats, or loss of blood glucose control. If you take both medications
together, tell your doctor if you have any of these symptoms. You may need a dose adjustment or
need your blood pressure checked more often to safely use both medications. 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.

MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers
may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in
patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and
arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting
diuretics.

MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is
recommended during coadministration. Patients should be advised to seek medical assistance if
they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood
glucose control.

References
 1. Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA "Nadolol in combination with
indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol 28 (1985): 29-33
2. "Product Information. Lozol (indapamide)." Rhone-Poulenc Rorer, Collegeville, PA.
3. Marcy TR, Ripley TL "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst
Pharm 63 (2006): 49-58

View all 5 references

Switch to consumer interaction data

Moderate

amlodipine bisoprolol

Applies to: amlodipine, bisoprolol

Bisoprolol and amLODIPine may have additive effects in lowering your blood pressure and
heart rate. You may experience headache, dizziness, lightheadedness, fainting, and/or changes in
pulse or heart beat. These side effects are most likely to be seen at the beginning of treatment,
following a dose increase, or when treatment is restarted after an interruption. Let your doctor
know if you develop these symptoms and they do not go away after a few days or they become
troublesome. You may need a dose adjustment or more frequent monitoring by your doctor to
safely use both medications. Avoid driving or operating hazardous machinery until you know
how the medications affect you, and use caution when getting up from a sitting or lying position.
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.

MONITOR: Additive reductions in heart rate, cardiac conduction, and cardiac contractility may
occur when calcium channel blockers are used concomitantly with beta blockers, particularly in
patients with ventricular or conduction abnormalities. While this combination may be useful and
effective in some situations, potentially serious cardiovascular adverse effects such as congestive
heart failure, severe hypotension, and/or exacerbation of angina may occur. The proposed
mechanisms include additive slowing in AV conduction, reduced cardiac contractility secondary
to beta-blockade, and decreased peripheral vascular resistance secondary to calcium channel
blockade. In addition, some calcium channel blockers may inhibit the CYP450 metabolism of
hepatically metabolized beta blockers, resulting in increased serum concentrations.

MANAGEMENT: Close clinical monitoring of patient hemodynamic response and tolerance is

recommended if a calcium channel blocker is prescribed with a beta blocker, and the dosage of
one or both agents adjusted as necessary. The same precaution should be observed when beta
blocker ophthalmic solutions are used, since they are systemically absorbed and can produce
clinically significant systemic effects even at low or undetectable plasma levels.

References
 1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta
blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
2. Pouleur H, Etienne J, Van Mechelen H, et al "Effects of nicardipine or nifedipine added to
propranolol in patients with coronary artery disease." Postgrad Med J 60 (1984): 23-8
3. Schoors DF, Vercruysse I, Musch G, Massart DL, Dupont AG "Influence of nicardipine on the
pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers." Br J Clin
Pharmacol 29 (1990): 497-501

View all 27 references

Switch to consumer interaction data

Minor

aspirin omeprazole

Applies to: aspirin, omeprazole

Consumer information for this minor interaction is not currently available. Some minor drug
interactions may not be clinically relevant in all patients. Minor drug interactions do not usually
cause harm or require a change in therapy. However, your healthcare provider can determine if
adjustments to your medications are needed.

Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin
and other salicylates. The interaction has been studied with omeprazole and aspirin, although
data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11
healthy volunteers led to a significant and progressively greater reduction in the mean serum
salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose).
The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin,
thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no
effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels,
skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy
volunteers. However, these results do not exclude the possibility that omeprazole might interfere
with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been
demonstrated in rats.

Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated
formulations due to premature disruption of the coating and intragastric release of the drug
secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20
mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets
but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate
tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the
risk of gastric adverse effects associated with salicylates.

References
 1. Nefesoglu FZ, Ayanoglu-Dulger G, Ulusoy NB, Imeryuz N "Interaction of omeprazole with enteric-
coated salicylate tablets." Int J Clin Pharmacol Ther 36 (1998): 549-53
2. Anand BS, Sanduja SK, Lichetenberger LM "Effect of omeprazole on the bioavailability of aspirin:
a randomized controlled study on healthy volunteers." Gastroenterology 116 (1999): A371
3. Inarrea P, Esteva F, Cornudella R, Lanas A "Omeprazole does not interfere with the antiplatelet
effect of low-dose aspirin in man." Scand J Gastroenterol 35 (2000): 242-6

Switch to consumer interaction data

Minor

hydrochlorothiazide amlodipine

Applies to: hydrochlorothiazide, amlodipine

Consumer information for this minor interaction is not currently available. Some minor drug
interactions may not be clinically relevant in all patients. Minor drug interactions do not usually
cause harm or require a change in therapy. However, your healthcare provider can determine if
adjustments to your medications are needed.

The antihypertensive effect of amlodipine and thiazide diuretics may be additive. Management
consists of monitoring blood pressure during coadministration, especially during the first 1 to 3
weeks of therapy.

References

1. Kaplan NM "Amlodipine in the treatment of hypertension." Postgrad Med J 67 Suppl 5 (1991):

s15-9

Switch to consumer interaction data

Minor

aspirin bisoprolol

Applies to: aspirin, bisoprolol

Consumer information for this minor interaction is not currently available. Some minor drug
interactions may not be clinically relevant in all patients. Minor drug interactions do not usually
cause harm or require a change in therapy. However, your healthcare provider can determine if
adjustments to your medications are needed.

High doses of salicylates may blunt the antihypertensive effects of beta-blockers. The proposed
mechanism is inhibition of prostaglandin synthesis. Low-dose aspirin does not appear to affect
blood pressure. In addition, beta-blockers may exert an antiplatelet effect, which may be additive
with the effects of some salicylates. Metoprolol may also increase aspirin absorption and/or
plasma concentrations of salicylates; however, the clinical significance of this effect is unknown.
Data have been conflicting. Until more information is available, patients who require
concomitant therapy should be monitored for altered antihypertensive response whenever a
salicylate is introduced or discontinued, or when its dosage is modified.

References

1. Keber I, Jerse M, Keber D, Stegnar M "The influence of combined treatment with propranolol
and acetylsalicylic acid on platelet aggregation in coronary heart disease." Br J Clin Pharmacol 7
(1979): 287-91
2. Spahn H, Langguth P, Kirch W, et al "Pharmacokinetics of salicylates administered with
metoprolol." Arzneimittelforschung 36 (1986): 1697-9
3. Sziegoleit W, Rausch J, Polak G, et al "Influence of acetylsalicylic acid on acute circulatory effects
of the beta-blocking agents pindolol and propranolol in humans." Int J Clin Pharmacol Ther
Toxicol 20 (1982): 423-30

Drug and food interactions

Minor

amlodipine food

Applies to: amlodipine

Consumer information for this minor interaction is not currently available. Some minor drug
interactions may not be clinically relevant in all patients. Minor drug interactions do not usually
cause harm or require a change in therapy. However, your healthcare provider can determine if
adjustments to your medications are needed.

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, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin
Pharmacol 46 (1998): 101-10

View all 6 references

Drug Interaction Classification

The classifications below are a guideline only. The relevance of a particular drug interaction to a specific
patient is difficult to determine using this tool alone given the large number of variables that may apply.

Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the
Major
benefit.

Moderately clinically significant. Usually avoid combinations; use it only under special
Moderate
circumstances.

Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug,
Minor
take steps to circumvent the interaction risk and/or institute a monitoring plan.

Unknown No information available.

Monitor Closely

 methylprednisolone + levofloxacin

methylprednisolone and levofloxacin both increase Other (see comment). Use

Caution/Monitor. Coadministration of quinolone antibiotics and corticosteroids may
increase risk of tendon rupture.

Interactions between your drugs

Major

methylprednisolone levofloxacin

Applies to: methylprednisolone, levofloxacin

LevoFLOXacin and other medications in its class can cause tendinitis and tendon rupture, and
the risk may be increased when combined with a steroid such as methylPREDNISolone. Older
adults over 60 years of age and those who have received a kidney, heart, and/or lung transplant
may be particularly susceptible. Tendon rupture can occur during or up to several months after
finishing levoFLOXacin treatment and may require surgery or result in prolonged disability.
Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe
alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring
to safely use both medications. Stop taking levoFLOXacin and call your doctor immediately if
you experience pain, swelling, or inflammation of a tendon area such as the back of the ankle,
shoulder, biceps, hand, or thumb. You should also avoid exercise or use of the affected area until
further instruction from your doctor. 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.

MONITOR CLOSELY: Concomitant administration of corticosteroids may potentiate the risk of

tendinitis and tendon rupture associated with fluoroquinolone treatment. The mechanism is
unknown. Tendinitis and tendon rupture have most frequently involved the Achilles tendon,
although cases involving the rotator cuff (the shoulder), the hand, the biceps, and the thumb have
also been reported. Some have required surgical repair or resulted in prolonged disability.
Tendon rupture can occur during or up to several months after completion of fluoroquinolone
therapy.

MANAGEMENT: Caution is recommended if fluoroquinolones are prescribed in combination

with corticosteroids, particularly in patients with other concomitant risk factors (e.g., age over 60
years; recipient of kidney, heart, and/or lung transplant). Patients should be advised to stop
taking the fluoroquinolone, avoid exercise and use of the affected area, and promptly contact
their physician if they experience pain, swelling, or inflammation of a tendon. In general,
fluoroquinolones should only be used to treat conditions that are proven or strongly suspected to
be caused by bacteria and only if the benefits outweigh the risks.

References

1. Khaliq Y, Zhanel GG "Fluoroquinolone-Associated Tendinopathy: A Critical Review of the

Literature." Clin Infect Dis 36 (2003): 1404-1410
2. FDA. U.S. Food and Drug Administration "Information for Healthcare Professionals.
Fluoroquinolone Antimicrobial Drugs. FDA Alert [7/8/2008]. Available from: URL:
http://www.fda.gov/cder/drug/InfoSheets/HCP/fluoroquinolonesHCP.htm." ([7/8/2008]):
3. "Product Information. Avelox (moxifloxacin)" Bayer, West Haven, CT.
4. van der Linden PD, Sturkenboom MC, Herings RM, Leufkens HM, Rowlands S, Stricker BH
"Increased risk of achilles tendon rupture with quinolone antibacterial use, especially in elderly
patients taking oral corticosteroids." Arch Intern Med 163 (2003): 1801-7
5. "Product Information. Levaquin (levofloxacin)." Ortho Pharmaceutical Corporation, Raritan, NJ.
6. "Product Information. Cipro (ciprofloxacin)." Bayer, West Haven, CT.
7. "Product Information. Baxdela (delafloxacin)." Melinta Therapeutics, Lincolnshire, IL.

Switch to consumer interaction dat

Moderate

albuterol levofloxacin

Applies to: albuterol, levofloxacin

Using albuterol together with levoFLOXacin can increase the risk of an irregular heart rhythm
that may be serious and potentially life-threatening, although it is a rare side effect. You may be
more susceptible if you have a heart condition called congenital long QT syndrome, other
cardiac diseases, conduction abnormalities, or electrolyte disturbances (for example, magnesium
or potassium loss due to severe or prolonged diarrhea or vomiting). The risk may exist even
when albuterol or similar medications are given by oral inhalation directly into the lungs, and
more so if these products are overused. Do not exceed the dose and frequency of use
recommended on the product label or prescribed by your doctor. Talk to your doctor if you have
any questions or concerns. Your doctor may already be aware of the risks, but has determined
that this is the best course of treatment for you and has taken appropriate precautions and is
monitoring you closely for any potential complications. You should seek immediate medical
attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or heart
palpitations during treatment with these medications. 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.

MONITOR: Beta-2 adrenergic agonists can cause dose-related prolongation of the QT interval
and potassium loss. Theoretically, coadministration with other agents that can prolong the QT
interval may result in additive effects and increased risk of ventricular arrhythmias including
torsade de pointes and sudden death. In general, the risk of an individual agent or a combination
of agents causing ventricular arrhythmia in association with QT prolongation is largely
unpredictable but may be increased by certain underlying risk factors such as congenital long QT
syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In
addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s)
involved and dosage(s) of the drug(s). Clinically significant prolongation of QT interval and
hypokalemia occur infrequently when beta-2 agonists are inhaled at normally recommended
dosages. However, these effects may be more common when the drugs are administered
systemically or when recommended dosages are exceeded.

MANAGEMENT: Caution is recommended if beta-2 agonists are used in combination with

other drugs that can prolong the QT interval. Patients should be advised to seek prompt medical
attention if they experience symptoms that could indicate the occurrence of torsade de pointes
such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of
breath, or syncope.
Minor

methylprednisolone albuterol

Applies to: methylprednisolone, albuterol

Consumer information for this minor interaction is not currently available. Some minor drug
interactions may not be clinically relevant in all patients. Minor drug interactions do not usually
cause harm or require a change in therapy. However, your healthcare provider can determine if
adjustments to your medications are needed.

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists
and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes
cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular
arrhythmias including torsade de pointes. However, clinical data are limited, and the potential
significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2
agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater
risk of developing hypokalemia.

Drug and food interactions

Moderate

cetirizine food

Applies to: cetirizine

Alcohol can increase the nervous system side effects of cetirizine such as dizziness, drowsiness,
and difficulty concentrating. Some people may also experience impairment in thinking and
judgment. You should avoid or limit the use of alcohol while being treated with cetirizine. Do
not use more than the recommended dose of cetirizine, and avoid activities requiring mental
alertness such as driving or operating hazardous machinery until you know how the medication
affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

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.

Moderate

methylprednisolone food

Applies to: methylprednisolone

Grapefruit juice may increase the blood levels and effects of certain medications such as
methylPREDNISolone. You may want to limit your consumption of grapefruit and grapefruit
juice during treatment with methylPREDNISolone. However, if you have been regularly
consuming grapefruit or grapefruit juice with methylPREDNISolone, do not alter the amounts of
these products in your diet without first talking to your doctor or other healthcare professional.
Contact your doctor if your condition changes or you experience increased side effects. Orange j

uice is not expected to interact.

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 primarily 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 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.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of levofloxacin.
According to the drug product labeling, administration of levofloxacin 500 mg with food prolonged the
time to peak concentration by 1 hour and decreased the Cmax decreased by 25% following
administration of the oral solution and by 14% following administration of the oral tablet.

MANAGEMENT: To ensure maximal and consistent oral absorption, levofloxacin oral solution should be
taken at least one hour before or two hours after meals. For administration of the oral solution with
continuous enteral nutrition, some experts recommend that the tube feeding should be interrupted for
one hour before and two hours after the dose of levofloxacin. The oral tablets may be taken without
regard to food.

Moderate

levofloxacin food

Applies to: levofloxacin

When levoFLOXacin as the oral solution is given with enteral (tube) feedings, levoFLOXacin
may not work as well. You could interrupt the feeding for 1 hour before and 2 hours after the
levoFLOXacin dose. However, this still may not entirely avoid the interaction and may not
always be feasible. LevoFLOXacin oral tablets may be taken without regard to food. 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.