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Drug Interactions between aliskiren / amlodipine / hydrochlorothiazide and Hypaque Cysto

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

hydroCHLOROthiazide diatrizoate

Applies to: aliskiren / amlodipine / hydrochlorothiazide and Hypaque Cysto (diatrizoate)

MONITOR: Forced diuresis during administration of radiocontrast agents may increase the risk of renal impairment in patients who are at high risk for contrast-induced nephropathy. Patients considered at high risk include those with diabetes (especially diabetic nephropathy), preexisting renal insufficiency (serum creatinine >1.5 mg/dL or GFR <60 mL/min/1.73 m2), volume depletion, advanced age (>70 years), congestive heart failure, and/or concurrent use of nephrotoxic drugs (e.g., NSAIDs). Diuretics have been studied for use in the prevention of contrast-induced nephropathy because investigators theorized that they may reduce medullary ischemia by decreasing oxygen demands. In published studies, however, maintenance intravenous fluids plus forced diuresis with furosemide, mannitol, or a combination of both given at the time of radiocontrast exposure generally produced similar or even higher rates of nephropathy compared with intravenous fluids alone. Meta-analyses of published data suggest that furosemide-based interventions significantly increase the risk of contrast-induced nephropathy compared with hydration alone, and one study found that hospitalization for all patients who developed contrast-induced nephropathy was increased by 4 days in those who received concomitant diuretic therapy. Contrast-induced nephropathy is most commonly defined as an increase in serum creatinine >=0.5 mg/dL or 25% from baseline within 48 to 72 hours of intravascular contrast administration in the absence of alternative etiologies, although nephropathy may occur up to a week after contrast exposure. While the condition is usually transient and asymptomatic, it can be associated with increased risk of renal failure, dialysis, prolonged hospitalization, significant long-term morbidity, and mortality.

MANAGEMENT: Whenever possible, alternative imaging techniques should be considered in patients who are at high risk for contrast-induced nephropathy. Otherwise, some experts recommend discontinuing diuretics 1 to 2 days before administration of contrast media, depending on the clinical feasibility of doing so. The smallest effective dose of a nonionic, hypo- or iso-osmolar contrast medium (e.g., iohexol, iodixanol, iopamidol) should be used, since the risk of nephropathy is increased with increasing contrast dose and/or osmolarity. Repeat procedures with contrast media, if necessary, should not occur until at least 72 hours after the previous contrast exposure and renal function has fully recovered. Although it is not necessary to measure the serum creatinine levels of every patient before contrast administration, measurements should generally be made in patients receiving contrast agent by intraarterial administration (which is associated with increased risk of nephropathy relative to intravenous administration) and patients with a history of kidney disease, proteinuria, kidney surgery, diabetes, hypertension, gout, or other risk factors for nephropathy. Creatinine measurements should be continued for 24 to 48 hours after administration of contrast medium. It is important that patients be adequately hydrated with either saline or sodium bicarbonate.

References

  1. "Product Information. Lasix (furosemide)." sanofi-aventis PROD (2007):
  2. Weinstein J-M, Heyman S, Brezis M "Potential deleterious effect of furosemide in radiocontrast nephropathy." Nephron 62 (1992): 413-5
  3. Solomon R, Werner C, Mann D, D'Elia J, Silva P "Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents." N Engl J Med 331 (1994): 1416-20
  4. Costa N "Understanding contrast media." J Infus Nurs 27 (2004): 302-12
  5. Stevens MA, McCullough PA, Tobin KJ, et al. "A prospective randomized trial of prevention measures in patients at high risk for contrast nephropathy: results of the P.R.I.N.C.E. Study. Prevention of Radiocontrast Induced Nephropathy Clinical Evaluation." J Am Coll Cardiol 33 (1999): 403-11
  6. Barrett BJ, Parfrey PS "Clinical practice. Preventing nephropathy induced by contrast medium." N Engl J Med 354 (2006): 379-86
  7. Briguori C, Marenzi G "Contrast-induced nephropathy: Pharmacological prophylaxis." Kidney Int 69(S100) (2006): S30-S38
  8. Tepel M, Aspelin P, Lameire N "Contrast-induced nephropathy: a clinical and evidence-based approach." Circulation 113 (2006): 1799-806
  9. Meschi M, Detrenis S, Musini S, Strada E, Savazzi G "Facts and fallacies concerning the prevention of contrast medium-induced nephropathy." Crit Care Med 34 (2006): 2060-80
  10. Stacul F, Adam A, Becker CR, et al. "Strategies to reduce the risk of contrast-induced nephropathy." Am J Cardiol 98(6S1) (2006): 59-77
  11. Ho KM, Sheridan DJ "Meta-analysis of frusemide to prevent or treat acute renal failure." BMJ 333 (2006): 420
  12. Kelly AM, Dwamena B, Cronin P, Bernstein SJ, Carlos RC "Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy." Ann Intern Med 148 (2008): 284-94
  13. Venkataraman R "Can we prevent acute kidney injury?" Crit Care Med 36(4 Suppl) (2008): S166-71
  14. Fishman EK, Reddan D "What are radiologists doing to prevent contrast-induced nephropathy (CIN) compared with measures supported by current evidence? A survey of European radiologists on CIN associated with computed tomography." Acta Radiol 49 (2008): 310-20
  15. Massicotte A "Contrast medium-induced nephropathy: strategies for prevention." Pharmacotherapy 28 (2008): 1140-50
View all 15 references

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Moderate

amLODIPine diatrizoate

Applies to: aliskiren / amlodipine / hydrochlorothiazide and Hypaque Cysto (diatrizoate)

MONITOR: Coadministration of calcium channel blockers may increase the cardiovascular effects of ionic X-ray contrast media. The mechanism is unknown. A study involving 125 patients undergoing bolus contrast left ventriculography found that the hemodynamic effect of a bolus dose of an ionic agent (0.5 mL/kg of diatrizoate meglumine and diatrizoate sodium or diatrizoate meglumine and diatrizoate sodium with edetate calcium) was increased in 65 patients receiving nifedipine or diltiazem compared to 60 patients not receiving these drugs. In the patients receiving nifedipine or diltiazem in addition to ionic contrast, the hypotensive response occurred earlier (4.2 seconds versus 12.9 seconds), was more profound (maximal decrease in systolic arterial pressure was 48.5 mmHg versus 36.9 mmHg), and was more prolonged (62.3 seconds versus 36.4 seconds) than in the patients receiving ionic contrast alone. There was no difference in the hemodynamic effect of a nonionic contrast agent, iopamidol, used alone compared to nifedipine or diltiazem used in addition to iopamidol.

MANAGEMENT: Patients taking calcium channel blockers should be closely monitored for increased cardiovascular effects of ionic X-ray contrast media, such as hypotension. Use of a nonionic contrast agent, such as iopamidol, may be considered instead of ionic contrast where clinically appropriate.

References

  1. Morris DL, Wisneski JA, Gertz EW, et al. "Potentiation by nifedipine and diltiazem of the hypotensive response after contrast angiography." J Am Coll Cardiol 6 (1985): 785-91
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0

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Minor

hydroCHLOROthiazide amLODIPine

Applies to: aliskiren / amlodipine / hydrochlorothiazide and aliskiren / amlodipine / hydrochlorothiazide

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

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Drug and food interactions

Moderate

aliskiren food

Applies to: aliskiren / amlodipine / hydrochlorothiazide

GENERALLY AVOID: Coadministration with orange, apple, or grapefruit juice may significantly decrease the oral bioavailability and renin-inhibiting effect of aliskiren. The exact mechanism of interaction is unknown, but may include inhibition of OATP2B1-mediated influx of aliskiren in the small intestine, formation of insoluble complexes between fruit juice constituents and aliskiren, and/or increased ionization of aliskiren due to reduced intestinal pH. In 12 healthy volunteers, 200 mL of either orange juice or apple juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 80% and 60%, respectively, compared to water. Plasma renin activity was 87% and 67% higher at 24 hours postdose when aliskiren was administered with orange juice and apple juice, respectively, compared to water. No significant differences were observed in the blood pressure or heart rate between treatments. However, this may be due to the delayed onset of aliskiren's blood pressure-lowering effect, which would not be apparent following a single dose. A similar pharmacokinetic interaction has been reported with grapefruit juice. In 11 healthy volunteers, 200 mL of normal strength grapefruit juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren Cmax and AUC by 81% and 61%, respectively, but there was no change in plasma renin activity compared to water. A high degree of interpatient variability was observed with all three interactions.

MONITOR: High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren. According to the product labeling, administration of aliskiren with a high-fat meal decreased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) by 85% and 71%, respectively. In clinical trials, however, aliskiren was administered without a fixed requirement in relation to meals.

MANAGEMENT: To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals. Coadministration with orange, apple, or grapefruit juice should be avoided, especially if these juices are to be consumed on a regular basis or shortly before or after aliskiren dosing.

References

  1. "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals (2007):
  2. Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP "Clinical pharmacokinetics and pharmacodynamics of aliskiren." Clin Pharmacokinet 47 (2008): 515-31
  3. Tapaninen T, Neuvonen PJ, Niemi M "Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren." Clin Pharmacol Ther 88 (2010): 339-42
  4. Tapaninen T, Neuvonen PJ, Niemi M "Orange and apple juices greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren." Br J Clin Pharmacol 71 (2010): 718-26
View all 4 references

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Moderate

hydroCHLOROthiazide food

Applies to: aliskiren / amlodipine / 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 "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

amLODIPine food

Applies to: aliskiren / amlodipine / 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 "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

amLODIPine food

Applies to: aliskiren / amlodipine / hydrochlorothiazide

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

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. Moller IW "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth 59 (1987): 522-6
  3. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol 67 (1991): 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy 10 (1990): 247
  6. Woie L, Storstein L "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J 2 (1981): 239-42
  7. Morris DL, Goldschlager N "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA 249 (1983): 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol 27 (1987): 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20
  10. Bar-Or D, Gasiel Y "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed) 282 (1981): 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7
  12. McMillan R "Management of acute severe verapamil intoxication." J Emerg Med 6 (1988): 193-6
  13. Perkins CM "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J 2 (1978): 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol 17 (1980): 395-400
View all 14 references

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Minor

amLODIPine food

Applies to: aliskiren / amlodipine / hydrochlorothiazide

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. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  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
  4. Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL "Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine." Br J Clin Pharmacol 50 (2000): 455-63
  5. Josefsson M, Ahlner J "Amlodipine and grapefruit juice." Br J Clin Pharmacol 53 (2002): 405; discussion 406
  6. Kane GC, Lipsky JJ "Drug-grapefruit juice interactions." Mayo Clin Proc 75 (2000): 933-42
View all 6 references

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Therapeutic duplication warnings

No 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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