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Drug Interactions between Cleviprex and Inderal LA

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

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Interactions between your drugs

Moderate

propranolol clevidipine

Applies to: Inderal LA (propranolol) and Cleviprex (clevidipine)

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

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

References

  1. Henry M, Kay MM, Viccellio P (1985) "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med, 3, p. 334-6
  2. Rosenkranz B, Ledermann H, Frolich JC (1986) "Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers." J Cardiovasc Pharmacol, 8, p. 943-9
  3. Tateishi T, Nakashima H, Shitou T, et al. (1989) "Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol." Eur J Clin Pharmacol, 36, p. 67-70
  4. Oesterle SN, Alderman EL, Beier-Scott L, Bain DS, Rothman MT, Schroder JS (1986) "Diltiazem and propranolol in combination: hemodynamic effects following acute intravenous administration." Am Heart J, 111, p. 489-97
  5. Yust I, Hoffman M, Aronson RJ (1992) "Life-threatening bradycardic reactions due to beta blocker-diltiazem interactions." Isr J Med Sci, 28, p. 292-4
  6. Hartwell BL, Mark JB (1986) "Combinations of beta blockers and calcium channel blockers: a cause of malignant perioperative conduction disturbances?" Anesth Analg, 65, p. 905-7
  7. Hossack KF (1982) "Conduction abnormalities due to diltiazem." N Engl J Med, 307, p. 953-4
  8. Strauss WE, Egan T, McIntyre KM, Parisi AF (1985) "Combination therapy with diltiazem and propranolol: precipitation of congestive heart failure." Clin Cardiol, 8, p. 363-6
  9. Ohman KP, Weiner L, von Schenck H, Karlberg BE (1985) "Antihypertensive and metabolic effects of nifedipine and labetalol alone and in combination in primary hypertension." Eur J Clin Pharmacol, 29, p. 149-54
  10. Bauer LA, Murray K, Horn JR, et al. (1989) "Influence of nifedipine therapy on indocyanine green and oral propranolol pharmacokinetics." Eur J Clin Pharmacol, 37, p. 257-60
  11. Ronn O, Bengtsson B, Edgar B, Raner S (1985) "Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol." Drugs, 29, p. 16-25
  12. Sinclair NI, Benzie JL (1983) "Timolol eye drops and verapamil: a dangerous combination." Med J Aust, 1, p. 548
  13. Pringle SD, MacEwen CJ (1987) "Severe bradycardia due to interaction of timolol eye drops and verapamil." Br Med J, 294, p. 155-6
  14. Rocha P, Guerret M, David D, Marchand X, Kahn JC (1990) "Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment." Cardiovasc Drugs Ther, 4, p. 1525-32
  15. Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S (1987) "Pharmacokinetic interactions between felodipine and metoprolol." Eur J Clin Pharmacol, 31, p. 575-8
  16. Pouleur H, Etienne J, Van Mechelen H, et al. (1984) "Effects of nicardipine or nifedipine added to propranolol in patients with coronary artery disease." Postgrad Med J, 60, p. 23-8
  17. Schoors DF, Vercruysse I, Musch G, Massart DL, Dupont AG (1990) "Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers." Br J Clin Pharmacol, 29, p. 497-501
  18. Nievel JG, Havard CW, Douglas-Jones AP (1987) "Comparison of concomitant nicardipine hydrochloride and propranolol with propranolol alone in patients with essential hypertension." Eur J Clin Pharmacol, 33, p. 21-5
  19. Maclean D, Mitchell ET, Coulson RR, Fitzsimons TJ, McDevitt DG (1988) "Atenolol-nifedipine combinations compared to atenolol alone in hypertension: efficacy and tolerability." Br J Clin Pharmacol, 25, p. 425-31
  20. Leon MB, Rosing DR, Bonow RO, Epstein SE (1985) "Combination therapy with calcium-channel blockers and beta blockers for chronic stable angina pectoris." Am J Cardiol, 55, b69-80
  21. Packer M (1989) "Combined beta-adrenergic and calcium-entry blockage in angina pectoris." N Engl J Med, 320, p. 709-18
  22. Strauss WE, Parisi AF (1988) "Combines use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina." Ann Intern Med, 109, p. 570-81
  23. Levine MA, Ogilvie RI, Leenen FH (1988) "Pharmacokinetic and pharmacodynamic interactions between nisoldipine and propranolol." Clin Pharmacol Ther, 43, p. 39-48
  24. Anastassiades CJ (1980) "Nifedipine and beta-blocker drugs." Br Med J, 281, p. 1251-2
  25. Tateishi T, Ohashi K, Fujimura A, Ebihara A (1992) "The influence of diltiazem versus cimetidine on propranolol metabolism." J Clin Pharmacol, 32, p. 1099-104
  26. Vinceneux P, Canal M, Domart Y, Roux A, Cascio B, Orofiamma B, Larribaud J, Flouvat B, Carbon C (1986) "Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol." Int J Clin Pharmacol Ther Toxicol, 24, p. 153-8
  27. Takahashi H, Ohashi N, Motokawa K, Sato S, Naito H (1993) "Poisoning caused by the combined ingestion of nifedipine and metoprolol." J Toxicol Clin Toxicol, 31, p. 631-7
View all 27 references

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Drug and food interactions

Moderate

propranolol food

Applies to: Inderal LA (propranolol)

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or immediately following meals.

References

  1. Olanoff LS, Walle T, Cowart TD, et al. (1986) "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther, 40, p. 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ (1984) "Stable oral availability of sustained release propranolol when co-administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br J Clin Pharmacol, 17, s45-50

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Moderate

propranolol food

Applies to: Inderal LA (propranolol)

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35

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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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