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Drug Interaction Report

7 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

enalapril hydroCHLOROthiazide

Applies to: enalapril / hydrochlorothiazide, enalapril / hydrochlorothiazide

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. Reader C, Peyregne EA, Suarez LD (1983) "Amrinone therapy in congestive cardiomyopathy." Am Heart J, 105, p. 1045
  2. Fujimura A, Shimokawa Y, Ebihara A (1990) "Influence of captopril on urinary excretion of furosemide in hypertensive subjects." J Clin Pharmacol, 30, p. 538-42
  3. Funck-Brentano C, Chatellier G, Alexandre JM (1986) "Reversible renal failure after combined treatment with enalapril and furosemide in a patient with congestive heart failure." Br Heart J, 55, p. 596-8
  4. Weisser K, Schloos J, Jakob S, et al. (1992) "The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients." Eur J Clin Pharmacol, 43, p. 173-7
  5. Motwani JG, Fenwick MK, Morton JJ, Struthers AD (1992) "Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure." Circulation, 86, p. 439-45
  6. Burnakis TG, Mioduch HJ (1984) "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med, 144, p. 2371-2
  7. Murphy BF, Whitworth JA, Kincaid-Smith P (1984) "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics." Br Med J, 288, p. 844-5
  8. Thind GS (1985) "Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis." J Clin Hypertens, 1, p. 337-43
  9. Radley AS, Fitzpatrick RW (1987) "An evaluation of the potential interaction between enalapril and amiloride." J Clin Pharm Ther, 12, p. 319-23
  10. Champ JD (1993) "Case report: azotemia secondary to enalapril and diuretic use and the diagnosis of renovascular hypertension." Am J Med Sci, 305, p. 25-7
  11. Hume AL, Murphy JL, Lauerman SE (1989) "Angiotensin-converting enzyme inhibitor-induced cough." Pharmacotherapy, 9, p. 88-90
  12. Lee HB, Blaufox MD (1992) "Renal functional response to captopril during diuretic therapy." J Nucl Med, 33, p. 739-43
  13. DeQuattro V (1991) "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol, 14, iv28-32;
  14. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  15. McLay JS, McMurray JJ, Bridges AB, Fraser CG, Struthers AD (1993) "Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure." Am Heart J, 126, p. 879-86
  16. Sudoh T, Fujimura A, Shiga T, et al. (1993) "Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects." J Clin Pharmacol, 33, p. 640-3
  17. Lederle RM (1985) "Captopril and hydrochlorothiazide in the fixed combination multicenter trial." J Cardiovasc Pharmacol, 7, S63-9
  18. (2001) "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc
  19. Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG (1994) "Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition." Circulation, 90, p. 220-4
  20. (2001) "Product Information. Capoten (captopril)." Bristol-Myers Squibb
  21. (2001) "Product Information. Lexxel (enalapril-felodipine)." Astra-Zeneca Pharmaceuticals
  22. "Product Information. Zestril (lisinopril)." Astra-Zeneca Pharmaceuticals
  23. Cerner Multum, Inc. "Australian Product Information."
View all 23 references

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Moderate

doxycycline hydroCHLOROthiazide

Applies to: Mondoxyne NL (doxycycline), enalapril / hydrochlorothiazide

MONITOR: The coadministration of diuretics with tetracyclines may result in decreased renal function and abnormalities in electrolytes and acid-base balance. As a class, tetracyclines can cause anti-anabolic effects which have led to increased blood urea nitrogen (BUN), azotemia, acidosis, and hyperphosphatemia. Diuretics have the potential to cause electrolyte and metabolic abnormalities, as well as worsen renal function. When used together, it is possible that these two classes of medications could have additive adverse effects.

MANAGEMENT: Patients on concomitant therapy with tetracycline antibiotics and diuretics should have their renal function and electrolytes monitored closely. The risk of additive adverse effects on the patient's renal function, electrolytes, and acid-base balance differs depending on the type of diuretic being used, the specific tetracycline antibiotic, and the clinical status of the patient. The manufacturer's labeling should be consulted for more specific recommendations.

References

  1. Jick H, Slone D, Shapiro S, et al. (1972) "Tetracycline and drug-attributed rises in blood urea nitrogen: a report from the Boston Collaborative Drug Surveillance Program." JAMA, 220, p. 377-9
  2. Garty M, Hurwitz A (1980) "Effect of cimetidine and antacids on gastrointestinal absorption of tetracycline." Clin Pharmacol Ther, 28, p. 203-7
  3. Tannenberg AM (1972) "Tetracycline and rises in urea nitrogen." JAMA, 221, p. 713
  4. Alexander MR (1972) "Tetracycline and rises in urea nitrogen." JAMA, 221, p. 713-4
  5. (2022) "Product Information. Xerava (eravacycline)." PAION Deutschland GmbH
  6. (2021) "Product Information. Xerava (eravacycline)." Tetraphase Pharmaceuticals, Inc
  7. (2022) "Product Information. Ospolot (sulthiame)." Phebra Pty Ltd, 10
  8. (2022) "Product Information. AcetaZOLAMIDE (acetaZOLAMIDE)." Mylan Institutional (formerly UDL Laboratories)
  9. (2021) "Product Information. AMILoride Hydrochloride (aMILoride)." Padagis
  10. (2020) "Product Information. Spironolactone (spironolactone)." Amneal Pharmaceuticals
  11. (2022) "Product Information. Kerendia (finerenone)." Bayer Pharmaceutical Inc
  12. (2021) "Product Information. Eplerenone (eplerenone)." Westminster Pharmaceuticals LLC
View all 12 references

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Drug and food interactions

Moderate

enalapril food

Applies to: enalapril / hydrochlorothiazide

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. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  2. Good CB, McDermott L (1995) "Diet and serum potassium in patients on ACE inhibitors." JAMA, 274, p. 538
  3. Ray K, Dorman S, Watson R (1999) "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens, 13, p. 717-20

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Moderate

enalapril food

Applies to: enalapril / hydrochlorothiazide

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

hydroCHLOROthiazide food

Applies to: enalapril / hydrochlorothiazide

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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Moderate

doxycycline food

Applies to: Mondoxyne NL (doxycycline)

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ (1976) "Interactions with the absorption of tetracyclines." Drugs, 11, p. 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R (1972) "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand, 191, p. 409-11
  3. Venho VM, Salonen RO, Mattila MJ (1978) "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol, 14, p. 277-80
  4. (2002) "Product Information. Minocin (minocycline)." Lederle Laboratories
  5. Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
  6. Bateman FJ (1970) "Effects of tetracyclines." Br Med J, 4, p. 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K (1970) "Interference of iron with the absorption of tetracyclines in man." Br Med J, 4, p. 532-4
  8. Greenberger NJ (1971) "Absorption of tetracyclines: interference by iron." Ann Intern Med, 74, p. 792-3
  9. Neuvonen PJ, Penttila O (1974) "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol, 7, p. 361-3
  10. (2018) "Product Information. Seysara (sarecycline)." Allergan Inc
  11. (2018) "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc.
View all 11 references

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Minor

doxycycline food

Applies to: Mondoxyne NL (doxycycline)

Chronic alcohol consumption may enhance the elimination of doxycycline. The mechanism is induction of hepatic microsomal enzymes by alcohol. In one study, the half-life of doxycycline in six alcoholics was 10.5 hours, compared with 14.7 hours in six control patients. In addition, half the alcoholic patients had serum concentrations below what is generally considered the minimum therapeutic concentration (0.5 mcg/mL) at 12 to 24 hours after the dose. The investigators suggest that twice-a-day dosing may be indicated in these patients, especially if additional inducing drugs are used. The elimination of other tetracyclines probably is not affected by alcohol consumption.

References

  1. Neuvonen PJ, Penttila O, Roos M, Tirkkonen J (1976) "Effect of long-term alcohol consumption on the half-life of tetracycline and doxycycline in man." Int J Clin Pharmacol Biopharm, 14, p. 303-7

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Therapeutic duplication warnings

No duplication warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
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 interaction information available.

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.