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Drug Interactions between Adenocard and Papacon

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

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Major

adenosine papaverine

Applies to: Adenocard (adenosine) and Papacon (papaverine)

MONITOR CLOSELY: Intracoronary administration of papaverine has been associated with QT interval prolongation and torsade de pointes (TdP) arrhythmia. The risk may theoretically increase in patients receiving concomitant medications that can also prolong the QT interval or cause bradycardia. QT interval prolongation has not been reported following systemic or intracavernosal administration of papaverine. The precise mechanism of papaverine-induced ventricular tachyarrhythmias has not been delineated, but may involve inhibition of potassium currents and prolongation of the action potential duration. In a study involving 182 consecutive patients undergoing fractional flow reserve measurements, premature ventricular beats occurred in 15.9% of patients following administration of intracoronary papaverine. TdP occurred in 2.8% of patients, and of those, 1.7% developed ventricular fibrillation. The incidence of intracoronary papaverine-induced ventricular tachyarrhythmias has not been determined, but has ranged between <0.67% and 8.8% following intracoronary administration of 6 mg to 20 mg. Based on numerous reports, female gender, hypokalemia, alkalosis, bradycardia, administration of papaverine into the left coronary artery, and a prior history of drug-induced QT prolongation may be risk factors for papaverine-induced fatal ventricular tachyarrhythmias. Apart from isolated case reports, there are no published data regarding the potential interaction between intracoronary papaverine and its use with other QT-prolonging drugs. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drugs involved and dosages of the drugs.

MANAGEMENT: Caution and close monitoring are advised during intracoronary administration of papaverine, particularly in patients receiving concomitant drugs that can prolong the QT interval or cause bradycardia and in patients with other risk factors described above. Some QT prolonging medications have specific monitoring, dosing, and/or other recommendations present in their labeling to help mitigate or monitor this side effect; therefore, it may be advisable to consult the package labeling of the concomitant medication if coadministration with intracoronary papaverine is being considered or deemed necessary.

References

  1. Nakayama M, Tanaka N, Sakoda K, et al. (2015) "Papaverine-induced polymorphic ventricular tachycardia during coronary flow reserve study of patients with moderate coronary artery disease." Circ J, 79, p. 530-6
  2. Goto M, Sato M, Kitzazawa H, et al. (2014) "Papaverine-induced QT interval prolongation and ventricular fibrillation in a patient with a history of drug-induced QT prolongation." Intern Med, 53, p. 1629-31
  3. Nakayama M, Saito A, Kitazawa H, et al. (2012) "Papaverine-induced polymorphic ventricular tachycardia in relation to QTU and giant T-U waves in four cases." Intern Med, 51, p. 351-6
  4. Inoue T, Asahi S, Takayanagi K, Morooka S, Takabatake Y (1994) "QT prolongation and possibility of ventricular arrhythmias after intracoronary papaverine." Cardiology, 84, p. 9-13
  5. Vrolix M, Piessens J, De Geest H (1991) "Torsades de pointes after intracoronary papaverine." Eur Heart J, 12, p. 273-6
  6. Kern MJ, Deligonul U, Serota H, Gudipati C, Buckingham T (1990) "Ventricular arrhythmia due to intracoronary papaverine: analysis of QT intervals and coronary vasodilatory reserve." Cathet Cardiovasc Diagn, 19, p. 229-36
  7. Talman CL, Winniford MD, Rossen JD, Simonetti I, Kienzle MG, Marcus ML (1990) "Polymorphous ventricular tachycardia: a side effect of intracoronary papaverine." J Am Coll Cardiol, 15, p. 275-8
  8. Jain A, Jenkins MG (1989) "Intracoronary electrocardiogram during torsade des pointes secondary to intracoronary papaverine." Cathet Cardiovasc Diagn, 18, p. 255-7
View all 8 references

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Drug and food interactions

Moderate

adenosine food

Applies to: Adenocard (adenosine)

ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives (e.g., theophylline) are nonspecific, competitive antagonists of adenosine receptors and may interfere with the hemodynamic effects of adenosine. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort.

MANAGEMENT: Clinicians should be aware that adenosine may be less effective in the presence of xanthine derivatives including caffeine. Patients should avoid consumption of caffeine-containing products for at least 12 hours, preferably 24 hours, prior to administration of adenosine for myocardial perfusion imaging.

References

  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  3. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  4. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  5. "Multum Information Services, Inc. Expert Review Panel"
  6. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
View all 6 references

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Moderate

papaverine food

Applies to: Papacon (papaverine)

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

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Moderate

adenosine food

Applies to: Adenocard (adenosine)

ADJUST DOSING INTERVAL: Methylxanthines (e.g., caffeine, theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the pharmacologic effects of adenosine and other adenosine receptor agonists such as dipyridamole and regadenoson. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort. Similarly, caffeine has been found to reduce the hemodynamic response to dipyridamole, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Clinicians should be aware that adenosine and other adenosine receptor agonists may be less effective in the presence of methylxanthines. Methylxanthines including caffeine should be withheld for 12 to 24 hours (or five half-lives) prior to administration of adenosine receptor agonists for myocardial perfusion imaging. However, parenteral aminophylline should be readily available for treating severe or persistent adverse reactions to adenosine receptor agonists such as bronchospasm or chest pain.

References

  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Aengevaeren WR, Corstens FH, Thien T (1989) "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med, 30, p. 1723-6
  3. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  4. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  5. (2002) "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim
  6. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  7. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group (1990) "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation, 81, p. 1205-9
  8. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
  9. (2008) "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc
View all 9 references

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Minor

adenosine food

Applies to: Adenocard (adenosine)

Nicotine may enhance adenosine-associated tachycardia and chest pain. The mechanism is not known. No special precautions appear to be necessary.

References

  1. Smits P, Eijsbouts A, Thien T (1989) "Nicotine enhances the circulatory effects of adenosine in human beings." Clin Pharmacol Ther, 46, p. 272-8
  2. Sylven C, Beermann B, Kaijser L, Jonzon B (1990) "Nicotine enhances angina pectoris-like chest pain and atriovenricular blockade provoked by intravenous bolus of adenosine in healthy volunteers." J Cardiovasc Pharmacol, 16, p. 962-5

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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.

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