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Drug Interaction Report

Drug interactions for the following 7 drug(s):

My Interactions List (Unsaved)

fenofibrate

glyburide

hydrochlorothiazide

ibuprofen

lisinopril

metformin

Glucosamine & Chondroitin with MSM (chondroitin / glucosamine / methylsulfonylmethane)

Interactions between your drugs

Moderate
ibuprofen glyburide
Applies to: ibuprofen, glyburide
MONITOR: The hypoglycemic effect of insulin secretagogues (e.g., sulfonylureas, meglitinides) may be potentiated by
certain drugs, including ACE inhibitors, amylin analogs, anabolic steroids, fibrates, monoamine oxidase inhibitors
(MAOIs, including linezolid), nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, selective serotonin reuptake
inhibitors (SSRIs), sulfonamides, disopyramide, propoxyphene, quinine, quinidine, and ginseng. These drugs may
increase the risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, fibrates, ginseng); stimulating insulin
secretion (salicylates, NSAIDs, disopyramide, quinine, quinidine, MAOIs, ginseng); increasing peripheral glucose
utilization (SSRIs, insulin-like growth factor); inhibiting gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor);
slowing the rate of gastric emptying (amylin analogs); and/or suppressing postprandial glucagon secretion (amylin
analogs). Or, they may increase plasma concentration of insulin secretagogues by displacing them from plasma
protein binding sites and/or inhibiting their metabolism (fibrates, NSAIDs, salicylates, sulfonamides). Clinical
hypoglycemia has been reported during use of some of these agents alone or with insulin and/or sulfonylureas. Use of
SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are
coadministered with insulin secretagogues, particularly in patients with advanced age and/or renal impairment. The
oral antidiabetic dosage(s) may require adjustment if an interaction is suspected. Patients should be apprised of the
signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness,
sweating, palpitations), how to treat it, and to contact their doctor if it occurs. Patients should be observed for loss of
glycemic control when these drugs are withdrawn.

References
1. Christensen LK, Hansen JM, Kristensen M "Sulphaphenazole-induced hypoglycemic attacks in tolbutamide-treated diabetics." Lancet 2 (1963):
1298-301
2. Turtle JR, Burgess JA "Hypoglycemic action of fenfluramine in diabetes mellitus." Diabetes 22 (1973): 858-67
3. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V "Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.)
with a depressed ginsenoside profile does not affect postprandial glycemia." Eur J Clin Nutr 57 (2003): 243-8

View all 101 references

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Moderate
ibuprofen hydrochlorothiazide
Applies to: ibuprofen, hydrochlorothiazide
MONITOR: Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics may adversely affect
renal function due to NSAID inhibition of the renal synthesis of prostaglandins that help maintain renal perfusion in
dehydrated states. The risk may be increased in patients on dietary sodium restriction. At the same time, hypotensive
effect of the diuretics may be reduced because inhibition of prostaglandins can lead to unopposed pressor activity
and, consequently, elevation in blood pressure. Natriuretic and diuretic effects may also be reduced, as NSAIDs have
been reported to cause sodium and water retention, which may account for the increased risk of congestive heart
failure associated with the combination. One study showed an increase in the incidence density of congestive heart
failure (in patients over 55 years of age) from 9.3 per 1,000 person-years in patients on diuretics to 23.3 per 1,000
person-years in patients on both diuretic and NSAID therapy. NSAIDs may also increase the risk of hyperkalemia
associated with potassium-sparing diuretics.

MANAGEMENT: In patients receiving both diuretic and NSAID therapy, management consists of avoiding dehydration
and carefully monitoring the patient's renal function and blood pressure. If renal insufficiency or hyperkalemia
develops, both drugs should be discontinued until the condition is corrected.

References
1. McCarthy JT, Torres VE, Romero JC, et al "Acute intrinsic renal failure induced by indomethacin." Mayo Clin Proc 57 (1982): 289-96
2. Bennett WM "Drug interactions and consequences of sodium restriction." Am J Clin Nutr 65 (1997): S678-81
3. Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV "Influence of meloxicam on furosemide pharmacokinetics and
pharmacodynamics in healthy volunteers." Eur J Clin Pharmacol 48 (1995): 247-51

View all 26 references

Moderate
glyburide hydrochlorothiazide
Applies to: glyburide, hydrochlorothiazide
MONITOR: The efficacy of insulin and other antidiabetic agents may be diminished by certain drugs, including atypical
antipsychotics, corticosteroids, diuretics, estrogens, gonadotropin-releasing hormone agonists, human growth
hormone, phenothiazines, progestins, protease inhibitors, sympathomimetic amines, thyroid hormones, asparaginase,
copanlisib, danazol, diazoxide, isoniazid, megestrol, omacetaxine, pegaspargase, phenytoin, temsirolimus, as well as
pharmacologic dosages of nicotinic acid and adrenocorticotropic agents. These drugs may interfere with blood
glucose control because they can cause hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or
exacerbation of preexisting diabetes.

MANAGEMENT: Caution is advised when drugs that can interfere with glucose metabolism are prescribed to patients
with diabetes. Close clinical monitoring of glycemic control is recommended following initiation or discontinuation of
these drugs, and the dosages of concomitant antidiabetic agents adjusted as necessary. Patients should be advised to
notify their physician if their blood glucose is consistently high or if they experience symptoms of severe
hyperglycemia such as excessive thirst and increases in the volume or frequency of urination. Likewise, patients should
be observed for hypoglycemia when these drugs are withdrawn from their therapeutic regimen.

References
1. Jori A, Carrara MC "On the mechanism of the hyperglycaemic effect of chlorpromazine." J Pharm Pharmacol 18 (1966): 623-4
2. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM "Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion." Arch
Int Pharmacodyn Ther 253 (1981): 154-63
3. "Product Information. Amaryl (glimepiride)." Hoechst Marion-Roussel Inc, Kansas City, MO.

View all 83 references

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ibuprofen lisinopril
Applies to: ibuprofen, lisinopril
MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effects of ACE
inhibitors. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in
unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects
blood pressure. Some NSAIDs may also alter the pharmacokinetics of certain ACE inhibitors. For example, oxaprozin
has been shown to reduce the systemic exposure (AUC) of enalapril and its active metabolite, enalaprilat.

MONITOR: Concomitant use of NSAIDs and ACE inhibitors may cause deterioration in renal function, particularly in
patients who are elderly or volume-depleted (including those on diuretic therapy) or have compromised renal
function. Acute renal failure may occur, although effects are usually reversible. Chronic use of NSAIDs alone may be
associated with renal toxicities, including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal
papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. Additionally, in patients with
prerenal conditions whose renal perfusion may be dependent on the function of prostaglandins, NSAIDs may
precipitate overt renal decompensation via a dose-related inhibition of prostaglandin synthesis. ACE inhibitors can
further worsen renal function by blocking the effect of angiotensin II-mediated efferent arteriolar vasoconstriction,
thereby decreasing glomerular filtration.

MANAGEMENT: Patients receiving ACE inhibitors who require prolonged (greater than 1 week) concomitant therapy
with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of
dosage of the NSAID. Renal function should also be evaluated periodically during prolonged coadministration. The
interaction is not expected to occur with low doses (e.g., low-dose aspirin) or intermittent short-term administration
of NSAIDs.

References
1. Townend JN, Doran J, Lote CJ, Davies MK "Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure
and interactions with captopril." Br Heart J 73 (1995): 434-41
2. Silberbauer K, Stanek B, Templ H "Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition." Br J Clin
Pharmacol 14 (1982): s87-93
3. Ahmad S "Indomethacin-enalapril interaction: an alert." South Med J 84 (1991): 411-2

View all 13 references

Moderate
glyburide lisinopril
Applies to: glyburide, lisinopril
MONITOR: The hypoglycemic effect of insulin secretagogues (e.g., sulfonylureas, meglitinides) may be potentiated by
certain drugs, including ACE inhibitors, amylin analogs, anabolic steroids, fibrates, monoamine oxidase inhibitors
(MAOIs, including linezolid), nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, selective serotonin reuptake
inhibitors (SSRIs), sulfonamides, disopyramide, propoxyphene, quinine, quinidine, and ginseng. These drugs may
increase the risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, fibrates, ginseng); stimulating insulin
secretion (salicylates, NSAIDs, disopyramide, quinine, quinidine, MAOIs, ginseng); increasing peripheral glucose
utilization (SSRIs, insulin-like growth factor); inhibiting gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor);
slowing the rate of gastric emptying (amylin analogs); and/or suppressing postprandial glucagon secretion (amylin
analogs). Or, they may increase plasma concentration of insulin secretagogues by displacing them from plasma
protein binding sites and/or inhibiting their metabolism (fibrates, NSAIDs, salicylates, sulfonamides). Clinical
hypoglycemia has been reported during use of some of these agents alone or with insulin and/or sulfonylureas. Use of
SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are
coadministered with insulin secretagogues, particularly in patients with advanced age and/or renal impairment. The
oral antidiabetic dosage(s) may require adjustment if an interaction is suspected. Patients should be apprised of the
signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness,
sweating, palpitations), how to treat it, and to contact their doctor if it occurs. Patients should be observed for loss of

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glycemic control when these drugs are withdrawn.

References
1. Christensen LK, Hansen JM, Kristensen M "Sulphaphenazole-induced hypoglycemic attacks in tolbutamide-treated diabetics." Lancet 2 (1963):
1298-301
2. Turtle JR, Burgess JA "Hypoglycemic action of fenfluramine in diabetes mellitus." Diabetes 22 (1973): 858-67
3. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V "Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.)
with a depressed ginsenoside profile does not affect postprandial glycemia." Eur J Clin Nutr 57 (2003): 243-8

View all 101 references

Moderate
hydrochlorothiazide lisinopril
Applies to: hydrochlorothiazide, lisinopril
MONITOR: Although they are frequently combined in clinical practice, diuretics and angiotensin converting enzyme
(ACE) inhibitors may have additive effects. Coadministration makes hypotension and hypovolemia more likely than
does either drug alone. Some ACE inhibitors may attenuate the increase in the urinary excretion of sodium caused by
some loop diuretics. Some patients on diuretics, especially those on dialysis or a dietary salt restriction, may
experience acute hypotension with lightheadedness and dizziness after receiving the first dose of the ACE inhibitor. In
addition, ACE inhibitors may cause renal insufficiency or acute renal failure in patients with sodium depletion or renal
artery stenosis.

MANAGEMENT: Monitoring of blood pressure, diuresis, electrolytes, and renal function is recommended during
coadministration. The possibility of first-dose hypotensive effects may be minimized by initiating therapy with small
doses of the ACE inhibitor, or either discontinuing the diuretic temporarily or increasing the salt intake approximately
one week prior to initiating an ACE inhibitor. Alternatively, the patient may remain under medical supervision for at
least two hours after the first dose of the ACE inhibitor, or until blood pressure has stabilized.

References
1. Murphy BF, Whitworth JA, Kincaid-Smith P "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics."
Br Med J 288 (1984): 844-5
2. Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG "Effect of intense angiotensin II suppression on the diuretic response to
furosemide during chronic ACE inhibition." Circulation 90 (1994): 220-4
3. "Product Information. Lexxel (enalapril-felodipine)." Astra Pharmaceuticals, Wayne, PA.

View all 23 references

Moderate
hydrochlorothiazide metformin
Applies to: hydrochlorothiazide, metformin
MONITOR: Diuretic-induced renal impairment and dehydration may increase the risk of lactic acidosis in patients who
are concomitantly taking metformin. In addition, thiazides and other diuretics may interfere with glucose control by
causing hyperglycemia, glucose intolerance, new-onset diabetes mellitus, and/or exacerbation of preexisting diabetes.

MANAGEMENT: Close clinical monitoring is recommended if diuretics are coadministered with antidiabetic agents.
Patients should be advised to monitor their blood glucose and to promptly notify their doctor if they experience
possible signs of lactic acidosis (such as malaise, myalgia, respiratory distress, hyperventilation, slow or irregular
heartbeat, somnolence, abdominal upset) or loss of glycemic control. Dose adjustments of metformin may be
required. Likewise, patients should be observed for hypoglycemia if diuretics are withdrawn from their therapeutic
regimen.

References

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1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

2. Cerner Multum, Inc. "Australian Product Information." O 0
3. "Multum Information Services, Inc. Expert Review Panel"

View all 4 references

Moderate
lisinopril metformin
Applies to: lisinopril, metformin
MONITOR: Limited data suggest that ACE inhibitors may potentiate the hypoglycemic effects of oral antidiabetic
drugs, including metformin. The mechanism is unknown. Symptomatic and sometimes severe hypoglycemia has
occurred.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if ACE inhibitors are
coadministered with metformin, particularly in patients with advanced age and/or renal impairment. Dosage
adjustments may be required if an interaction is suspected. Patients should be apprised of the signs and symptoms of
hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness, sweating, palpitations), how to
treat it, and to contact their physician if it occurs. Patients should be observed for loss of glycemic control when ACE
inhibitors are withdrawn.

References
1. "Product Information. Altace (ramipril)." Hoechst Marion-Roussel Inc, Kansas City, MO.

Moderate
glyburide fenofibrate
Applies to: glyburide, fenofibrate
MONITOR: The hypoglycemic effect of insulin secretagogues (e.g., sulfonylureas, meglitinides) may be potentiated by
certain drugs, including ACE inhibitors, amylin analogs, anabolic steroids, fibrates, monoamine oxidase inhibitors
(MAOIs, including linezolid), nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates, selective serotonin reuptake
inhibitors (SSRIs), sulfonamides, disopyramide, propoxyphene, quinine, quinidine, and ginseng. These drugs may
increase the risk of hypoglycemia by enhancing insulin sensitivity (ACE inhibitors, fibrates, ginseng); stimulating insulin
secretion (salicylates, NSAIDs, disopyramide, quinine, quinidine, MAOIs, ginseng); increasing peripheral glucose
utilization (SSRIs, insulin-like growth factor); inhibiting gluconeogenesis (SSRIs, MAOIs, insulin-like growth factor);
slowing the rate of gastric emptying (amylin analogs); and/or suppressing postprandial glucagon secretion (amylin
analogs). Or, they may increase plasma concentration of insulin secretagogues by displacing them from plasma
protein binding sites and/or inhibiting their metabolism (fibrates, NSAIDs, salicylates, sulfonamides). Clinical
hypoglycemia has been reported during use of some of these agents alone or with insulin and/or sulfonylureas. Use of
SSRIs has also been associated with loss of awareness of hypoglycemia in isolated cases.

MANAGEMENT: Close monitoring for the development of hypoglycemia is recommended if these drugs are
coadministered with insulin secretagogues, particularly in patients with advanced age and/or renal impairment. The
oral antidiabetic dosage(s) may require adjustment if an interaction is suspected. Patients should be apprised of the
signs and symptoms of hypoglycemia (e.g., headache, dizziness, drowsiness, nausea, hunger, tremor, weakness,
sweating, palpitations), how to treat it, and to contact their doctor if it occurs. Patients should be observed for loss of
glycemic control when these drugs are withdrawn.

References
1. Christensen LK, Hansen JM, Kristensen M "Sulphaphenazole-induced hypoglycemic attacks in tolbutamide-treated diabetics." Lancet 2 (1963):
1298-301
2. Turtle JR, Burgess JA "Hypoglycemic action of fenfluramine in diabetes mellitus." Diabetes 22 (1973): 858-67
3. Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V "Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.)
with a depressed ginsenoside profile does not affect postprandial glycemia." Eur J Clin Nutr 57 (2003): 243-8

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View all 101 references

No other interactions were found between your selected drugs.

Note: this does not necessarily mean no interactions exist. Always consult with your doctor or pharmacist.

Other drug and disease interactions

fenofibrate interacts with more than 60 other drugs and 7 diseases.
glyburide interacts with more than 400 other drugs and 6 diseases.
hydrochlorothiazide interacts with more than 400 other drugs and more than 10 diseases.
ibuprofen interacts with more than 200 other drugs and more than 10 diseases.
lisinopril interacts with more than 300 other drugs and 8 diseases.
metformin interacts with more than 200 other drugs and 4 diseases.
Glucosamine & Chondroitin with MSM (chondroitin / glucosamine / methylsulfonylmethane) interacts with 6
other drugs.

Drug and food interactions

Moderate
lisinopril food
Applies to: lisinopril
GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are
using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich
salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin
(RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high
or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

References
1. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a
potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20
2. "Product Information. Vasotec (enalapril)." Merck & Co, Inc, West Point, PA.
3. Good CB, McDermott L "Diet and serum potassium in patients on ACE inhibitors." JAMA 274 (1995): 538

Therapeutic duplication warnings

No therapeutic duplications were found for your selected drugs.

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.

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

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

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

Unknown No information available.

Do not stop taking any medications without consulting your healthcare provider.

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Disclaimer: Every effort has been made to ensure that the information provided by Multum is accurate, up-to-date and complete, but no guarantee
is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource
beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. Multum's information is a reference
resource designed as supplement to, and not a substitute for, the expertise, skill, knowledge, and judgement of healthcare practitioners in patient
care. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is
safe, effective, or appropriate for any given patient. Multum Information Services, Inc. does not assume any responsibility for any aspect of
healthcare administered with the aid of information Multum provides. Copyright 2000-2018 Multum Information Services, Inc. The information
contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects.
If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.

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