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Drug Interactions between EpiPen 2-Pak and Hemangeol

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

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Interactions between your drugs

Major

propranolol EPINEPHrine

Applies to: Hemangeol (propranolol) and EpiPen 2-Pak (epinephrine)

MONITOR CLOSELY: Noncardioselective beta-blockers can significantly enhance the pressor response to epinephrine. The mechanism involves blockade of beta-2 adrenergic receptors in the peripheral vasculature, resulting in unopposed alpha-adrenergic effect of epinephrine that is responsible for vasoconstriction. Severe hypertension accompanied by bradycardia has been reported in patients who were treated with a noncardioselective beta-blocker like propranolol or nadolol prior to receiving epinephrine. In rare cases, cardiac arrest and stroke have occurred. This interaction has not been reported with cardioselective beta-blockers, which generally have little effect on beta-2 adrenergic receptors at therapeutic dosages. In studies of hypertensive patients, treatment with propranolol was associated with significant increases in blood pressure and peripheral vascular resistance and decreases in heart rate and forearm blood flow in response to epinephrine administration, while metoprolol had only minor effects on epinephrine-induced cardiovascular changes compared to placebo. Similarly, in 24 healthy subjects treated with nadolol, atenolol, or placebo for one week prior to epinephrine administration, mean arterial pressure and calf vascular resistance increased significantly in the nadolol group but not in the atenolol group, and marked bradycardia also occurred in the former but not latter group. Theoretically, the interaction may also occur with noncardioselective beta-blocker ophthalmic preparations, since they may be systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

MONITOR CLOSELY: Beta-blockers may attenuate the response to epinephrine in the treatment of anaphylactic reactions. Noncardioselective beta-blockers, in particular, can antagonize the bronchodilating effects of epinephrine by blocking beta-2 adrenergic receptors in smooth muscles of the bronchial tree. All beta-blockers can antagonize the cardiostimulatory effects of epinephrine by blocking beta-1 adrenergic receptors in the heart. Some investigators have suggested that the use of beta-blockers in itself is associated with an increased incidence and severity of anaphylaxis due to modulation of adenylate cyclase, which can influence release of anaphylactogenic mediators. However, data are limited and conflicting.

MANAGEMENT: Extreme caution and close monitoring of cardiovascular status are indicated when epinephrine is administered to patients treated with noncardioselective beta-blockers. A dosage reduction of epinephrine may be necessary. Withdrawal of beta-blockers before anesthesia may increase the risk of myocardial ischemia and is not recommended. The interaction is not expected to occur with local anesthetics used in dental surgery that contain very low concentrations of epinephrine.

References

  1. Whelan TV "Propranolol, epinephrine, and accelerated hypertension during hemodialysis." Ann Intern Med 106 (1987): 327
  2. Gandy W "Severe epinephrine-propanolol interaction." Ann Emerg Med 18 (1989): 98-9
  3. van Herwaarden CL, Binkhorst RA, Fennis JF, van 't Laar A "Effects of adrenaline during treatment with propranolol and metoprolol." Br Med J 2 (1977): 1029
  4. Houben H, Thien TH, De Boo TH, et al. "Influence of selective and non-selective beta-adrenoceptor blockade on the haemodynamic effect of adrenaline during combined antihypertensive drug therapy." Clin Sci 57 (1979): s397-9
  5. van Herwaarden CL, Fennis JF, Binkhorst RA, van 't Laar A "Haemodynamic effects of adrenaline during treatment of hypertensive patients with propranolol and metoprolol." Eur J Clin Pharmacol 12 (1977): 397-402
  6. Hansbrough JF, Near A "Propranolol-epinephrine antagonism with hypertension and stroke." Ann Intern Med 92 (1980): 717
  7. Cryer PE, Rizza RA, Haymond MW, Gerich JE "Epinephrine and norepinephrine are cleared through beta-adrenergic, but not alpha-adrenergic, mechanisms in man." Metabolism 29 (1980): 1114-8
  8. Saff R, Nahhas A, Fink JN "Myocardial infarction induced by coronary vasospasm after self- administration of epinephrine." Ann Allergy 70 (1993): 396-8
  9. Larsen LS, Larsen A "Labetalol in the treatment of epinephrine overdose." Ann Emerg Med 19 (1990): 680-2
  10. Catalano PM "Possible interaction of epinephrine with propranolol." J Am Acad Dermatol 10 (1984): 839
  11. Spencer PS, Klein LE "Interaction of epinephrine and propranolol." J Am Acad Dermatol 14 (1986): 1093-4
  12. Foster CA, Aston SJ "Propranolol-epinephrine interaction: a potential disaster." Plast Reconstr Surg 72 (1983): 74-8
  13. Greenwald AE "Propranolol-epinephrine interaction." J Dermatol Surg Oncol 9 (1983): 713
  14. Goldberg I, Ashburn FS Jr, Palmberg PF, Kass MA, Becker B "Timolol and epinephrine: a clinical study of ocular interactions." Arch Ophthalmol 98 (1980): 484-6
  15. Alexander GD "Dangers of propranolol withdrawal prior to local anesthesia with epinephrine." Arch Otolaryngol 111 (1985): 280
  16. Reeves RA, Boer WH, DeLeve L, Leenen FH "Nonselective beta-blockade enhances pressor responsiveness to epinephrine, norepinephrine, and angiotensin II in normal man." Clin Pharmacol Ther 35 (1984): 461-6
  17. Dzubow LM "The interaction between propranolol and epinephrine as observed in patients undergoing Mohs' surgery." J Am Acad Dermatol 15 (1986): 71-5
  18. Richards DA, Prichard BN, Hernandez R "Circulatory effects of noradrenaline and adrenaline before and after labetalol." Br J Clin Pharmacol 7 (1979): 371-8
  19. Halloran TJ, Phillips CE "Propranolol intoxication. A severe case responding to norepinephrine therapy." Arch Intern Med 141 (1981): 810-1
  20. Chu D, Cocco G, Schweda E, Haeusler G, Strozzi C "Influence of propranolol and pindolol on the haemodynamic effects of papaverine, isoprenaline and noradrenaline in hypertensive patients." Eur J Clin Pharmacol 18 (1980): 141-6
  21. O'Grady J, Oh V, Turner P "Effects of propranolol and oxprenolol on the vasoconstrictor response to noradrenaline in the superficial hand vein in man." Eur J Clin Pharmacol 14 (1978): 83-5
  22. Fisher DA "Interaction of epinephrine and B-blockers." JAMA 274 (1995): 1830
  23. Jay GT, Chow MS "Interaction of epinephrine and B-blockers." JAMA 274 (1995): 1830-1
  24. Ponten J, Biber B, Bjuro T, Henriksson BA, Hjalmarson A, Lundberg D "Beta-receptor blockade and spinal anaesthesia. Withdrawal versus continuation of long-term therapy." Acta Anaesthesiol Scand Suppl 76 (1982): 62-9
  25. Centeno RF, Yu YL "The propanolol-epinephrine interaction revisited: a serious and potentially catastrophic adverse drug interaction in facial plastic surgery." Plast Reconstr Surg 111 (2003): 944-5
View all 25 references

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Drug and food interactions

Moderate

propranolol food

Applies to: Hemangeol (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: Hemangeol (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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Moderate

EPINEPHrine food

Applies to: EpiPen 2-Pak (epinephrine)

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

References

  1. Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res 1 (1979): 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther 11 (1970): 656
  3. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  4. "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals PROD (2001):
  5. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  6. "Product Information. Focalin (dexmethylphenidate)." Mikart Inc (2001):
  7. "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company (2002):
View all 7 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.

Further information

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

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