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Drug Interactions between Inderal LA and metocurine

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

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Interactions between your drugs

Moderate

propranolol metocurine

Applies to: Inderal LA (propranolol) and metocurine

MONITOR: Neuromuscular blocking agents and beta-blockers may have additive cardiovascular depressant effects. In one study, 8 of 42 patients receiving beta-blockers developed bradycardia (less than 50 bpm) and hypotension (systolic BP less than 80 mmHg) when atracurium was administered. Most of these patients were under general anesthesia using diazepam, methohexital, droperidol, fentanyl, and nitrous oxide/oxygen. In isolated case reports, patients treated with timolol eye drops have developed bradycardia and hypotension when atracurium or alcuronium was administered. The interaction has also been reported with atenolol and atracurium.

MONITOR: Limited data suggest that beta-blockers may modestly potentiate the pharmacologic effects of neuromuscular blocking agents. The exact mechanism of interaction is unknown but may involve effects in the postsynaptic membrane, as beta-blockers alone have been reported to exacerbate or unmask myasthenia gravis. In one case report, two thyrotoxic patients treated with propranolol 120 mg/day for 14 days prior to surgery demonstrated prolonged neuromuscular blockade with tubocurarine. Likewise, eight study subjects receiving esmolol (300 to 500 mcg/kg/min) five minutes before induction of anesthesia experienced an approximately 3-minute delay in recovery from succinycholine-induced neuromuscular blockade relative to subjects receiving a placebo infusion. Other studies have not corroborated these findings. A study of 16 patients receiving chronic therapy (at least one month) with various beta-blockers found no significant difference in the onset and duration of action of rocuronium compared to 27 patients in the control group. Earlier studies even found a slight reduction in the effect of succinylcholine in patients treated with propranolol intravenously before surgery and a shorter duration of action of tubocurarine in patients administered propranolol or oxprenolol. Esmolol has been reported to delay the onset of action of rocuronium from 93 to 118 seconds.

MANAGEMENT: Clinicians should recognize the potential for altered effects of neuromuscular blocking agents in the presence of beta-blockers. Respiratory and cardiovascular status should be closely monitored.

References

  1. Glynne GL "Drug interaction?" Anaesthesia 39 (1984): 293
  2. Yate B, Mostafa SM "Drug interaction?" Anaesthesia 39 (1984): 728-9
  3. Herishanu Y, Rosenberg P "Beta-blockers and myasthenia gravis." Ann Intern Med 83 (1975): 834-5
  4. Murthy VS, Patel KD, Elangovan RG, Hwang TF, Solochek SM, Steck JD, Laddu AR "Cardiovascular and neuromuscular effects of esmolol during induction of anesthesia." J Clin Pharmacol 26 (1986): 351-7
  5. Harrah MD, Way WL, Katzung BG "The interaction of d-tubocurarine with antiarrhythmic drugs." Anesthesiology 33 (1970): 406-10
  6. Rozen MS, Whan FM "Prolonged curarization associated with propranolol." Med J Aust 1 (1972): 467-8
  7. Chapple DJ, Clark JS, Hughes R "Interaction between atracurium and drugs used in anaesthesia." Br J Anaesth 55 Suppl 1 (1983): s17-22
  8. Loan PB, Connolly FM, Mirakhur RK, Kumar N, Farling P "Neuromuscular effects of rocuronium in patients receiving beta-adrenoreceptor blocking, calcium entry blocking and anticonvulsant drugs." Br J Anaesth 78 (1997): 90-1
View all 8 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. "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther 40 (1986): 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "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 (1984): 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 "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 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.

Further information

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