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Drug Interactions between Rythmol SR and Toprol-XL

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

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Interactions between your drugs

Moderate

metoprolol propafenone

Applies to: Toprol-XL (metoprolol) and Rythmol SR (propafenone)

MONITOR: Propafenone may significantly increase serum levels and effects of some oral beta-blockers. The proposed mechanism is inhibition of CYP450 2D6 first-pass metabolism and decreased hepatic clearance. Data are available for metoprolol and propranolol only; however, other hepatically metabolized oral beta-blockers may also be affected. Renally excreted beta-blockers such as atenolol, carteolol, nadolol, or sotalol are not expected to interact. In addition, negative inotropic effects may be potentiated.

MANAGEMENT: Patients receiving this combination should be monitored for hypotension, heart failure, bradycardia, arrhythmias, and mental status changes. Beta-blocker dosage may be decreased if necessary.

References

  1. Wagner F, Kalusche D, Trenk D, et al. (1987) "Drug interaction between propafenone and metoprolol." Br J Clin Pharmacol, 24, p. 213-20
  2. Stagni G, Davis PJ, Ludden TM (1991) "Human pharmacokinetics of betaxolol enantiomers." J Pharm Sci, 80, p. 321-4
  3. Janku I, Perlik F, Tkaczykova M, Brodanova M (1992) "Disposition kinetics and concentration-effect relationship of metipranolol in patients with cirrhosis and healthy subjects." Eur J Clin Pharmacol, 42, p. 337-40
  4. Ahmad S (1991) "Metoprolol-induced delirium perpetuated by propafenone." Am Fam Physician, 44, 1142,4
  5. Piquette-Miller M, Foster RT, Kappagoda CT, Jamali F (1992) "Effect of aging on the pharmacokinetics of acebutolol enantiomers." J Clin Pharmacol, 32, p. 148-56
  6. Smith RL (1985) "Polymorphic metabolism of the beta-adrenoreceptor blocking drugs and its clinical relevance." Eur J Clin Pharmacol, 28, p. 77-84
  7. McGourty JC, Silas JH, Fleming JJ, McBurney A, Ward JW (1985) "Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin." Clin Pharmacol Ther, 38, p. 409-13
  8. Le Coz F, Sauleman P, Poirier JM, Cuche JL, Midavaine M, Rames A, Lecocq B, Jaillon P (1991) "Oral pharmacokinetics of bisoprolol in resting and exercising healthy volunteers." J Cardiovasc Pharmacol, 18, p. 28-34
  9. Amemiya M, Tabei K, Furuya H, Sakairi Y, Asano Y (1992) "Pharmacokinetics of carteolol in patients with impaired renal function." Eur J Clin Pharmacol, 43, p. 417-21
  10. Barbey JT (1991) "Clinical pharmacology and beta-blocking efficacy of propafenone." J Cardiovasc Pharmacol, 17, s41-3
  11. Kowey PR, Kirsten EB, Fu CJ, Mason WD (1989) "Interaction between propranolol and propafenone in healthy volunteers." J Clin Pharmacol, 29, p. 512-7
  12. Wagner F, Kalusche D, Trenk D, Jahnchen E, Roskamm H (1987) "Drug interaction between propafenone and metoprolol." Br J Clin Pharmacol, 24, p. 213-20
  13. (2002) "Product Information. Tenormin (atenolol)." ICN Pharmaceuticals Inc
  14. (2002) "Product Information. Normodyne (labetalol)." Schering Corporation
  15. (2002) "Product Information. Corgard (nadolol)." Bristol-Myers Squibb
  16. (2001) "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories
  17. (2001) "Product Information. Blocadren (timolol)." Merck & Co., Inc
  18. (2001) "Product Information. Brevibloc (esmolol)." DuPont Pharmaceuticals
  19. "Product Information. Rythmol (propafenone)." Knoll Pharmaceutical Company
  20. (2001) "Product Information. Cartrol (carteolol)." Abbott Pharmaceutical
  21. (2001) "Product Information. Betapace (sotalol)." Berlex Laboratories
  22. (2001) "Product Information. Levatol (penbutolol)." Reed and Carnrick
  23. Morgan T (1994) "Clinical pharmacokinetics and pharmacodynamics of carvedilol." Clin Pharmacokinet, 26, p. 335-46
  24. McTavish D, Campoli-Richards D, Sorkin EM (1993) "Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy." Drugs, 45, p. 232-58
  25. Seffart G ed. (1991) "Drug Dosage in Renal Insufficiency." Dordrecht, South Holland, : Kluwer Academic Publishers
  26. Limbird LE eds., Gilman AG, Hardman JG (1995) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill
View all 26 references

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Drug and food interactions

Moderate

metoprolol food

Applies to: Toprol-XL (metoprolol)

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

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

References

  1. (2001) "Product Information. Lopressor (metoprolol)." Novartis Pharmaceuticals
  2. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54

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Moderate

propafenone food

Applies to: Rythmol SR (propafenone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK (1993) "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol, 43, p. 120-6
  2. (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
  3. (2023) "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated
  4. (2022) "Product Information. Propafenone (propafenone)." Accord-UK Ltd
View all 4 references

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Moderate

metoprolol food

Applies to: Toprol-XL (metoprolol)

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.

See also

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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.

Further information

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