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Summary of Symptoms

Drowsiness
Captopril and naproxen in combination may cause a symptom that is related to drowsiness
Captopril and allopurinol in combination may cause a symptom that is related to drowsiness
Gout-like arthritis
Captopril and allopurinol in combination may cause a symptom that is related to gout-like arthritis
Hearing loss
Levothyroxine and simvastatin in combination may cause a symptom that is related to hearing loss
Heart disease due to high blood pressure
Naproxen and hydrochlorothiazide in combination may cause a symptom that is related to heart disease due to high blood pressure
Swelling of the hands or feet
Naproxen and hydrochlorothiazide in combination may cause a symptom that is related to swelling of the hands or feet

       
 
Drowsiness
Captopril and naproxen in combination may cause the following symptom that is related to drowsiness:
  • Kidney failure
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Monitor blood pressure carefully if you are using both of these medications. Using these medications together may decrease the blood pressure-lowering effectiveness of the ACE inhibitor blood pressure medications and lead to increased blood pressure. Monitor blood pressure carefully if you are using both of these medications.

Long-term use of anti-inflammatory drug/s increases the chances of developing side effects. Long-term use of anti-inflammatory drug/s increases the chances of developing kidney inflammation, interstitial nephritis, acute tubular necrosis, kidney failure, nephrotic syndrome, abnormal kidney blood test - elevated "creatinine", renal papillary necrosis, abnormal kidney blood test - elevated "bun" or kidney damage. This drug combination of can affect kidney function.

Dose adjustments may be necessary. Blood pressure should be monitored regularly when this drug combination is taken for long periods of time. People should be observed more closely around the time that the anti-inflammatory drug/s is started or stopped, or when the dose is changed. Blood tests for kidney function should be monitored regularly in individuals who take both of these medications.
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Note: Original Source for Medical Professionals
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 increase the risk of renal impairment, particularly in volume-depleted patients. 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.

REFERENCE +

  1. Effect of propranolol and indomethacin on the depressor action of captopril in patients with essential hypertension. Seto S, Aoi W, Iwami K, et al Clin Exp Hypertens 1987;9:623-7.
  2. Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension. Moore TJ, Crantz FR, Hollenberg NK Hypertension 1981;3:168-73.
  3. Interaction of captopril and ibuprofen on glomerular and tubular function in humans. Allon M, Pasque CB, Rodriguez M Am J Physiol 1990;259:f233-8.
  4. Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients. Polonia J, Boaventura I, Gama G, Camoes I, Bernardo F, Andrade P, Nunes JP, Brandao F, Cerqueiragomes M J Hypertens 1995;13:925-31.
  5. Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril. Townend JN, Doran J, Lote CJ, Davies MK Br Heart J 1995;73:434-41.
  6. Product Information. Celebrex (celecoxib). Anonymous Searle, Chicago, IL. PROD;
  7. Indomethacin-enalapril interaction: an alert. Ahmad S South Med J 1991;84:411-2.
  8. Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition. Silberbauer K, Stanek B, Templ H Br J Clin Pharmacol 1982;14:s87-93.
  9. Product Information. Toradol (ketorolac). Anonymous Syntex Laboratories Inc, Palo Alto, CA. PROD;
  10. Hemodynamic and humoral interactions between perindopril and indomethacin in essential hypertensive subjects. Abdel-Haq B, Magagna A, Favilla S, Salvetti A J Cardiovasc Pharmacol 1991;18:s33-6.
  11. Interaction of indomethacin with felodipine and enalapril. Morgan T, Anderson A J Hypertens 1993;11:S338-9.
  12. Product Information. Daypro (oxaprozin). Anonymous Searle, Skokie, IL. PROD;
  13. Ibuprofen interferes with the efficacy of antihypertensive drugs: a randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen. Radack KL, Deck CC, Bloomfield SS Ann Intern Med 1987;107:628-35.
 
       
 
Drowsiness
Captopril and allopurinol in combination may cause the following symptom that is related to drowsiness:
  • Lethargy
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Patients who are taking captopril (captopril) and allopurinol (allopurinol) should be followed closely for signs of infection. Caution is advised if captopril (captopril) and allopurinol (allopurinol) are used together. People who are taking this drug combination should be followed closely. Serious side effects can occur with this drug combination. Cases of fatalities in individuals taking this drug combination have been reported in the medical literature. The following side effects have been mentioned in a case report: fast pulse/rapid heart rate that originates in the sinus node, nausea, hives, gout, breathing problems - tightening of the airways, significant decrease in blood pressure, generalized itching, thickening chest secretions, severe chest pain or bluish tone to fingers/toes due to lack of circulation. Some patients may experience the following side effects with the first dose of the enalapril: fast pulse/rapid heart rate that originates in the sinus node, nausea, hives, gout, breathing problems - tightening of the airways, significant decrease in blood pressure, generalized itching, thickening chest secretions, severe chest pain or bluish tone to fingers/toes due to lack of circulation. This medication combination may cause severe breathing problems due to closure of the airways.

Notify your physician if you develop: joint pain, lethargy, body pain, swelling of the tongue, skin rash, hives, sore throat/throat irritation, shortness of breath, swelling of the face, fever, tightness in the throat, infection, shaking chills, muscle pain/soreness, flu or cold-like symptoms or swelling of the lips.
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Note: Original Source for Medical Professionals
MONITOR CLOSELY: Coadministration of allopurinol with angiotensin converting enzyme (ACE) inhibitors has been associated with a risk of severe hypersensitivity reactions, neutropenia, agranulocytosis, and serious infections. The mechanism of interaction is unknown, but impaired renal function may be a predisposing factor. Case reports, albeit rare, have mostly involved captopril. Fever, myalgia, arthralgia, exfoliative dermatitis, and Stevens-Johnson syndrome (including one fatality) have been reported, with the latter occurring 3 to 5 weeks after initiation of allopurinol. In an isolated case involving enalapril, a man who had been receiving enalapril without incident developed generalized pruritus, urticaria, severe chest pain, severe nausea, peripheral cyanosis, hypotension, sinus tachycardia, and mild bronchospasm approximately 20 minutes after the first dose of allopurinol 100 mg prescribed for acute gout. Serial electrocardiograms and cardiac enzyme studies revealed evidence of acute myocardial infarction. Following recovery, the patient continued to take enalapril uneventfully without allopurinol. No pharmacokinetic interactions have been reported between allopurinol and ACE inhibitors. In a study of 12 healthy volunteers, allopurinol had no significant effect on the bioavailability of captopril.

MANAGEMENT: Caution is advised if allopurinol is prescribed in combination with an ACE inhibitor, particularly in the elderly and patients with renal impairment. Periodic monitoring of white blood cell counts is recommended. Patients should be advised to promptly discontinue these medications and seek medical attention if they develop dyspnea; throat constriction; swelling of the face, lips, or tongue; urticaria; rash; fever; arthralgia; or myalgia. Patients should also contact their physician if they notice signs of infection or experience fever, chills, sore throat, lethargy, body aches, or other flu-like symptoms.

REFERENCE +

  1. Fatal Stevens-Johnson syndrome in a patient on captopril and allopurinol. Pennell DJ, Nunan TO, O'Doherty MJ, Croft DN Lancet 1984;1:463.
  2. Product Information. Zyloprim capsules (allopurinol). Anonymous Glaxo Wellcome, Research Triangle Park, NC. PROD;
  3. EPARs. European Union Public Assessment Reports. Available from: URL: http://www.emea.eu.int/htms/human/epar/a.htm. EMEA. European Medicines Agency [1995-2007];
  4. Fever, myalgia, and arthralgia in a patient on captopril and allopurinol. Samanta A, Burden AC Lancet 1984;1:679.
  5. Pharmacokinetics of captopril in healthy subjects and in patients with cardiovascular diseases. Duchin KL, McKinstry DN, Cohen AI, Migdalof BH Clin Pharmacokinet 1988;14:241-59.
  6. Allopurinol and enalapril: drug induced anaphylactic coronary spasm and acute myocardial infarction. Ahmad S Chest 1995;108:586.
 
       
 
       
 
Gout-like arthritis (resembles the arthritis/joint inflammation caused by gout)
Captopril and allopurinol in combination may cause the following symptom that is related to gout-like arthritis:
  • Stevens-Johnson syndrome
Hide MORE...
Patients who are taking captopril (captopril) and allopurinol (allopurinol) should be followed closely for signs of infection. Caution is advised if captopril (captopril) and allopurinol (allopurinol) are used together. People who are taking this drug combination should be followed closely. Serious side effects can occur with this drug combination. Cases of fatalities in individuals taking this drug combination have been reported in the medical literature. The following side effects have been mentioned in a case report: fast pulse/rapid heart rate that originates in the sinus node, nausea, hives, gout, breathing problems - tightening of the airways, significant decrease in blood pressure, generalized itching, thickening chest secretions, severe chest pain or bluish tone to fingers/toes due to lack of circulation. Some patients may experience the following side effects with the first dose of the enalapril: fast pulse/rapid heart rate that originates in the sinus node, nausea, hives, gout, breathing problems - tightening of the airways, significant decrease in blood pressure, generalized itching, thickening chest secretions, severe chest pain or bluish tone to fingers/toes due to lack of circulation. This medication combination may cause severe breathing problems due to closure of the airways.

Notify your physician if you develop: joint pain, lethargy, body pain, swelling of the tongue, skin rash, hives, sore throat/throat irritation, shortness of breath, swelling of the face, fever, tightness in the throat, infection, shaking chills, muscle pain/soreness, flu or cold-like symptoms or swelling of the lips.
Hide SOURCE +

Note: Original Source for Medical Professionals
MONITOR CLOSELY: Coadministration of allopurinol with angiotensin converting enzyme (ACE) inhibitors has been associated with a risk of severe hypersensitivity reactions, neutropenia, agranulocytosis, and serious infections. The mechanism of interaction is unknown, but impaired renal function may be a predisposing factor. Case reports, albeit rare, have mostly involved captopril. Fever, myalgia, arthralgia, exfoliative dermatitis, and Stevens-Johnson syndrome (including one fatality) have been reported, with the latter occurring 3 to 5 weeks after initiation of allopurinol. In an isolated case involving enalapril, a man who had been receiving enalapril without incident developed generalized pruritus, urticaria, severe chest pain, severe nausea, peripheral cyanosis, hypotension, sinus tachycardia, and mild bronchospasm approximately 20 minutes after the first dose of allopurinol 100 mg prescribed for acute gout. Serial electrocardiograms and cardiac enzyme studies revealed evidence of acute myocardial infarction. Following recovery, the patient continued to take enalapril uneventfully without allopurinol. No pharmacokinetic interactions have been reported between allopurinol and ACE inhibitors. In a study of 12 healthy volunteers, allopurinol had no significant effect on the bioavailability of captopril.

MANAGEMENT: Caution is advised if allopurinol is prescribed in combination with an ACE inhibitor, particularly in the elderly and patients with renal impairment. Periodic monitoring of white blood cell counts is recommended. Patients should be advised to promptly discontinue these medications and seek medical attention if they develop dyspnea; throat constriction; swelling of the face, lips, or tongue; urticaria; rash; fever; arthralgia; or myalgia. Patients should also contact their physician if they notice signs of infection or experience fever, chills, sore throat, lethargy, body aches, or other flu-like symptoms.

REFERENCE +

  1. Fatal Stevens-Johnson syndrome in a patient on captopril and allopurinol. Pennell DJ, Nunan TO, O'Doherty MJ, Croft DN Lancet 1984;1:463.
  2. Product Information. Zyloprim capsules (allopurinol). Anonymous Glaxo Wellcome, Research Triangle Park, NC. PROD;
  3. EPARs. European Union Public Assessment Reports. Available from: URL: http://www.emea.eu.int/htms/human/epar/a.htm. EMEA. European Medicines Agency [1995-2007];
  4. Fever, myalgia, and arthralgia in a patient on captopril and allopurinol. Samanta A, Burden AC Lancet 1984;1:679.
  5. Pharmacokinetics of captopril in healthy subjects and in patients with cardiovascular diseases. Duchin KL, McKinstry DN, Cohen AI, Migdalof BH Clin Pharmacokinet 1988;14:241-59.
  6. Allopurinol and enalapril: drug induced anaphylactic coronary spasm and acute myocardial infarction. Ahmad S Chest 1995;108:586.
 
       
 
       
 
Hearing loss
Levothyroxine and simvastatin in combination may cause the following symptom that is related to hearing loss:
  • Underactive thyroid gland
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The following side effects have been mentioned in a case report: underactive thyroid gland or increased tsh levels. No special actions appear to be necessary when taking these drugs at recommended doses. This drug interaction appears to be rare. The dose of levothyroxine (levothyroxine) may need to be adjusted if an interaction is suspected. The dose of hormone may need to be adjusted if an interaction is suspected. These side effects have only occured in a few individuals.
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Note: Original Source for Medical Professionals
Rarely, lovastatin and simvastatin have been reported to reduce the pharmacologic effects of thyroid hormone. The exact mechanism of interaction is unknown. In isolated case reports, patients stabilized on levothyroxine developed symptoms of hypothyroidism and/or elevated thyroid-stimulating hormone (TSH) levels following the addition of lovastatin or simvastatin. Discontinuation of the statin led to resolution of symptoms and normalization of TSH levels. In one case, the patient was subsequently prescribed pravastatin without any adverse effects on his thyroid status. No particular intervention should be necessary when lovastatin or simvastatin is prescribed to patients receiving thyroid hormone therapy, since the interaction appears to be extremely rare. However, thyroid hormone dosage may need to be adjusted if an interaction is suspected. Alternatively, a switch to a statin with a different metabolic profile such as fluvastatin, pravastatin, or rosuvastatin may help.

REFERENCE +

  1. Interaction between simvastatin and L-thyroxine. Kisch E, Segall HS Ann Intern Med 2005;143:547.
  2. Drug interaction between thyroxine and lovastatin. Demke DM N Engl J Med 1989;321:1341-2.
 
       
 
       
 
Heart disease due to high blood pressure
Naproxen and hydrochlorothiazide in combination may cause the following symptom that is related to heart disease due to high blood pressure:
  • High blood pressure
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This drug combination of can affect kidney function. The combination of naproxen (naproxen) and hydrochlorothiazide (hydrochlorothiazide) can cause low blood pressure. Monitor blood pressure carefully if you are using both of these medications. Contact your physician if you develop symptoms of heart failure including: shortness of breath, swelling in the ankles/legs, fatigue, lack of energy, loss of appetite, or nausea. The risk of the following side effects may be increased: congestive heart failure. The risk of developing (or worsening) congestive heart failure/weakened heart is increased in patients taking these medications. One published article suggested that the chance of developing congestive heart failure may be increased by using this drug combination people age 55 or older, 9.3 or older, 1,000 or older, 23.3 or older. The risk of developing (or worsening) congestive heart failure/weakened heart is increased in patients taking these medications people age 55 or older, 9.3 or older, 1,000 or older, 23.3 or older. Taking these two drugs together can increase the blood levels of a substance called "potassium". Check with your physician immediately for any signs of increased potassium including weakness, lack of energy, irregular heartbeat, confusion, or tingling or a feeling of heaviness in the arms or legs.

Drink lots of fluids and avoid becoming dehydrated while taking this medication combination. Follow kidney function closely with regular blood tests when taking this drug combination. Kidney function may be evaluated with certain blood tests including a "BUN" and "creatinine".
Hide SOURCE +

Note: Original Source for Medical Professionals
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.

REFERENCE +

  1. Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers. Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV Eur J Clin Pharmacol 1995;48:247-51.
  2. Interaction of indomethacin with furosemide. Poe TE, Scott RB, Keith JF Jr J Fam Pract 1983;16:610-6.
  3. Interaction of triamterene-hydrochlorothiazide (T-H) and ibuprofen (I). Gehr T, Sica DA, Steigler BW, Marshall C Clin Pharmacol Ther 1990;47:200.
  4. Indomethacin- and Moduretic--induced hyperkalemia. Mor R, Pitlik S, Rosenfeld JB Isr J Med Sci 1983;19:535-7.
  5. Aldosterone antagonists in the treatment of heart failure. Marcy TR, Ripley TL Am J Health Syst Pharm 2006;63:49-58.
  6. Anuric renal failure precipitated by indomethacin and triamterene. Weinberg MS, Quigg RJ, Salant DJ, Bernard DB Nephron 1985;40:216-8.
  7. Reversible acute renal failure from combined triamterene and indomethacin. Favre L, Glasson P, Vallotton MB Ann Intern Med 1982;96:317-20.
  8. Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin. Watkins J, Abbot EC, Hensby CN, Webster J, Dollery CT Br Med J 1980;281:702-5.
  9. The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone. Ripley EB, Gehr TW, Wallace H, Wade J, Kish C, Sica DA Int J Clin Pharmacol Ther 1994;32:12-8.
  10. Interaction studies with bumetanide and furosemide: effects of probenecid and of indomethacin on response to bumetanide in man. Brater DC, Fox WR, Chennavasin P J Clin Pharmacol 1981;21:647-53.
  11. The effects of naproxen and sulindac on renal function and their interaction with hydrochlorothiazide and piretanide in man. Dixey JJ, Noormohamed FH, Lant AF, Brewerton DA Br J Clin Pharmacol 1987;23:55-63.
  12. Bumetanide-induced diuresis and natriuresis: effect of prostaglandin synthetase inhibition. Kaufman J, Hamburger R, Matheson J, Flamenbaum W J Clin Pharmacol 1981;21:663-7.
  13. Drug interactions and consequences of sodium restriction. Bennett WM Am J Clin Nutr 1997;65:S678-81.
  14. Drug interactions with diuretics. Leary WP, Reyes AJ S Afr Med J 1984;65:455-61.
  15. Attenuation of furosemide's diuretic effect by indomethacin: pharmacokinetic evaluation. Smith DE, Brater DC, Lin ET, Benet LZ J Pharmacokinet Biopharm 1979;7:265-74.
  16. The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons. Gurwitz JH, Everitt DE, Monane M, et al J Gerontol A Biol Sci Med Sci 1996;51:m74-9.
  17. Acute intrinsic renal failure induced by indomethacin. McCarthy JT, Torres VE, Romero JC, et al Mayo Clin Proc 1982;57:289-96.
  18. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A Arch Intern Med 1998;158:1108-12.
  19. Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension. Pedrinelli R, Magagna A, Arzilli F, et al Clin Pharmacol Ther 1980;28:722-31.
  20. Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications. Furst DE J Rheumatol Suppl 1988;17:58-62.
  21. Indomethacin-bumetanide interaction: an alert. Ahmad S Am J Cardiol 1984;54:246-7.
  22. Drug-induced hyperkalemia: old culprits and new offenders. Perazella MA Am J Med 2000;109:307-14.
  23. Interaction of diuretics and non-steroidal anti-inflammatory drugs in man. Favre L, Glasson P, Riondel A, Vallotton MB Clin Sci 1983;64:407-15.
  24. Product Information. HydroDIURIL (hydrochlorothiazide). Anonymous Merck & Co, Inc, West Point, PA. PROD;
  25. A comparative study of the action of frusemide and methyclothiazide on renin release by rat kidney slices and the interaction with indomethacin. Desaulles E, Schwartz J Br J Pharmacol 1979;65:193-6.
  26. Interaction between diuretics and indomethacin. Allan SG, Knox J, Kerr F Br Med J 1981;283:1611.
 
       
 
       
 
Swelling of the hands or feet
Naproxen and hydrochlorothiazide in combination may cause the following symptom that is related to swelling of the hands or feet:
  • Congestive heart failure
Hide MORE...
This drug combination of can affect kidney function. The combination of naproxen (naproxen) and hydrochlorothiazide (hydrochlorothiazide) can cause low blood pressure. Monitor blood pressure carefully if you are using both of these medications. Contact your physician if you develop symptoms of heart failure including: shortness of breath, swelling in the ankles/legs, fatigue, lack of energy, loss of appetite, or nausea. The risk of the following side effects may be increased: congestive heart failure. The risk of developing (or worsening) congestive heart failure/weakened heart is increased in patients taking these medications. One published article suggested that the chance of developing congestive heart failure may be increased by using this drug combination people age 55 or older, 9.3 or older, 1,000 or older, 23.3 or older. The risk of developing (or worsening) congestive heart failure/weakened heart is increased in patients taking these medications people age 55 or older, 9.3 or older, 1,000 or older, 23.3 or older. Taking these two drugs together can increase the blood levels of a substance called "potassium". Check with your physician immediately for any signs of increased potassium including weakness, lack of energy, irregular heartbeat, confusion, or tingling or a feeling of heaviness in the arms or legs.

Drink lots of fluids and avoid becoming dehydrated while taking this medication combination. Follow kidney function closely with regular blood tests when taking this drug combination. Kidney function may be evaluated with certain blood tests including a "BUN" and "creatinine".
Hide SOURCE +

Note: Original Source for Medical Professionals
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.

REFERENCE +

  1. Influence of meloxicam on furosemide pharmacokinetics and pharmacodynamics in healthy volunteers. Muller FO, Schall R, Devaal AC, Groenewoud G, Hundt HKL, Middle MV Eur J Clin Pharmacol 1995;48:247-51.
  2. Interaction of indomethacin with furosemide. Poe TE, Scott RB, Keith JF Jr J Fam Pract 1983;16:610-6.
  3. Interaction of triamterene-hydrochlorothiazide (T-H) and ibuprofen (I). Gehr T, Sica DA, Steigler BW, Marshall C Clin Pharmacol Ther 1990;47:200.
  4. Indomethacin- and Moduretic--induced hyperkalemia. Mor R, Pitlik S, Rosenfeld JB Isr J Med Sci 1983;19:535-7.
  5. Aldosterone antagonists in the treatment of heart failure. Marcy TR, Ripley TL Am J Health Syst Pharm 2006;63:49-58.
  6. Anuric renal failure precipitated by indomethacin and triamterene. Weinberg MS, Quigg RJ, Salant DJ, Bernard DB Nephron 1985;40:216-8.
  7. Reversible acute renal failure from combined triamterene and indomethacin. Favre L, Glasson P, Vallotton MB Ann Intern Med 1982;96:317-20.
  8. Attenuation of hypotensive effect of propranolol and thiazide diuretics by indomethacin. Watkins J, Abbot EC, Hensby CN, Webster J, Dollery CT Br Med J 1980;281:702-5.
  9. The effect of nonsteroidal agents (NSAIDs) on the pharmacokinetics and pharmacodynamics of metolazone. Ripley EB, Gehr TW, Wallace H, Wade J, Kish C, Sica DA Int J Clin Pharmacol Ther 1994;32:12-8.
  10. Interaction studies with bumetanide and furosemide: effects of probenecid and of indomethacin on response to bumetanide in man. Brater DC, Fox WR, Chennavasin P J Clin Pharmacol 1981;21:647-53.
  11. The effects of naproxen and sulindac on renal function and their interaction with hydrochlorothiazide and piretanide in man. Dixey JJ, Noormohamed FH, Lant AF, Brewerton DA Br J Clin Pharmacol 1987;23:55-63.
  12. Bumetanide-induced diuresis and natriuresis: effect of prostaglandin synthetase inhibition. Kaufman J, Hamburger R, Matheson J, Flamenbaum W J Clin Pharmacol 1981;21:663-7.
  13. Drug interactions and consequences of sodium restriction. Bennett WM Am J Clin Nutr 1997;65:S678-81.
  14. Drug interactions with diuretics. Leary WP, Reyes AJ S Afr Med J 1984;65:455-61.
  15. Attenuation of furosemide's diuretic effect by indomethacin: pharmacokinetic evaluation. Smith DE, Brater DC, Lin ET, Benet LZ J Pharmacokinet Biopharm 1979;7:265-74.
  16. The impact of ibuprofen on the efficacy of antihypertensive treatment with hydrochlorothiazide in elderly persons. Gurwitz JH, Everitt DE, Monane M, et al J Gerontol A Biol Sci Med Sci 1996;51:m74-9.
  17. Acute intrinsic renal failure induced by indomethacin. McCarthy JT, Torres VE, Romero JC, et al Mayo Clin Proc 1982;57:289-96.
  18. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Heerdink ER, Leufkens HG, Herings RM, Ottervanger JP, Stricker BH, Bakker A Arch Intern Med 1998;158:1108-12.
  19. Influence of indomethacin on the natriuretic and renin-stimulating effect of bumetanide in essential hypertension. Pedrinelli R, Magagna A, Arzilli F, et al Clin Pharmacol Ther 1980;28:722-31.
  20. Clinically important interactions of nonsteroidal antiinflammatory drugs with other medications. Furst DE J Rheumatol Suppl 1988;17:58-62.
  21. Indomethacin-bumetanide interaction: an alert. Ahmad S Am J Cardiol 1984;54:246-7.
  22. Drug-induced hyperkalemia: old culprits and new offenders. Perazella MA Am J Med 2000;109:307-14.
  23. Interaction of diuretics and non-steroidal anti-inflammatory drugs in man. Favre L, Glasson P, Riondel A, Vallotton MB Clin Sci 1983;64:407-15.
  24. Product Information. HydroDIURIL (hydrochlorothiazide). Anonymous Merck & Co, Inc, West Point, PA. PROD;
  25. A comparative study of the action of frusemide and methyclothiazide on renin release by rat kidney slices and the interaction with indomethacin. Desaulles E, Schwartz J Br J Pharmacol 1979;65:193-6.
  26. Interaction between diuretics and indomethacin. Allan SG, Knox J, Kerr F Br Med J 1981;283:1611.
 
       
 
 
NOTE: Just because a drug or combination of drugs can cause a symptom does not mean it is actually causing your symptom. Symptoms can be caused by medical conditions as well. Make sure that your physician is aware of any symptoms you are experiencing so he/she can work with you to determine the cause. Please DO NOT STOP MEDICATIONS without first consulting a physician since doing so could be hazardous to your health.
DISCLAIMER: Please note that the information DoubleCheckMD.com provides is intended to help individuals to work with their medical professionals and is for educational purposes only. It does not constitute medical or healthcare advice and serves to supplement, not substitute for, the expertise and judgment of a healthcare professional. In all cases individuals should consult with a physician before taking any action based on DoubleCheckMD feedback including, but not limited to ceasing taking any drug, changing diet or commencing or discontinuing any course of treatment. The information provided by DoubleCheckMD.com is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that the use of a particular drug is safe, appropriate or effective.


 
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