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Drug Interactions between adenosine / lidocaine / magnesium sulfate and Quelicin

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

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Interactions between your drugs

Moderate

lidocaine succinylcholine

Applies to: adenosine / lidocaine / magnesium sulfate and Quelicin (succinylcholine)

MONITOR: Neuromuscular-blocking effects may be potentiated when neuromuscular blocking agents are coadministered with local anesthetics, however, the mechanism is not completely understood. In one study of 10 healthy volunteers evaluating the use of regional anesthesia with intravenous prilocaine with (n=5) or without mivacurium (n=5), prolonged weakness was observed in subjects who received both prilocaine and mivacurium, compared to the control group. Another study of patients undergoing orthognathic surgery (n=16) evaluated the degree of neuromuscular blockade using the train of four (TOF) prior to induction and during maintenance anesthesia with propofol, fentanyl and rocuronium, with or without an oral mucosal injection of lidocaine 1% with epinephrine 10 mcg/mL (LE). The TOF ratio began to decrease 2 minutes after the injection of LE, reached a minimum value of approximately 3% twelve minutes after the injection, and then began to recover, indicating an increase in neuromuscular blockade when LE was administered with rocuronium compared to the control group. In another study of healthy patients (n=30), the effect of epidural bupivacaine on the duration, intensity, and reversal of atracurium-induced neuromuscular muscular blockade was evaluated. In the epidural bupivacaine group (n=15), the duration of neuromuscular blockade, time until first response to TOF, and reversal time were all significantly prolonged when compared to the control group. Clinical data for all neuromuscular blocking agents and local anesthetics are lacking.

MANAGEMENT: Monitoring for prolonged and/or enhanced neuromuscular blockade is advised if local anesthetics are coadministered with neuromuscular-blocking agents. Individual product labeling for the neuromuscular blocking agent should be consulted for specific recommendations and guidance.

References

  1. Pouttu J, Tuominen MK, Rosenberg PH (1988) "Cardiovascular responses caused by the combination of lidocaine and vecuronium in the induction of general anaesthesia." Acta Anaesthesiol Scand, 32, p. 549-52
  2. Fukuda S, Wakuta K, Ishikawa T, Oshita S, Sakabe T, Takeshita H (1987) "Lidocaine modifies the effect of succinylcholine on muscle oxygen consumption in dogs." Anesth Analg, 66, p. 325-8
  3. Matsuo S, Rao DBS, Chaudry I, Foldes FF (1978) "Interaction of muscle relaxants and local anesthetics at the neuromuscular junction." Anesth Analg, 57, p. 580-7
  4. Bruckner J, Thomas KC, Bikhazi GB, Foldes FF (1980) "Neuromuscular drug interactions of clinical importance." Anesth Analg, 59, p. 678-82
  5. Harrah MD, Way WL, Katzung BG (1970) "The interaction of d-tubocurarine with antiarrhythmic drugs." Anesthesiology, 33, p. 406-10
  6. Miller RD, Way WL (1971) "Inhibition of succinylcholine-induced increased intragastric pressure by nondepolarizing muscle relaxants and lidocaine." Anesthesiology, 34, p. 185-8
  7. (2019) "Product Information. Rocuronium Bromide (rocuronium)." Hospira Inc
  8. (2022) "Product Information. Anectine (succinylcholine)." Sandoz Inc
  9. (2024) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Inc.
  10. (2015) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Healthcare Corporation
  11. (2022) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hameln Pharma Ltd
  12. (2022) "Product Information. Xylocaine HCl (lidocaine)." Aspen Pharmacare Australia Pty Ltd
  13. Ninomiya A, Terakawa Y, Matsuura N, Ichinohe T, Kaneko Y (2024) Oral mucosal injection of a local anesthetic solution containing epinephrine enhances muscle relaxant effects of rocuronium https://pubmed.ncbi.nlm.nih.gov/22428970/
  14. Torrance JM, lewer bm, Galletly DC (2024) Low-dose mivacurium supplementation of prilocaine i.v. regional anaesthesia https://pubmed.ncbi.nlm.nih.gov/9068344/
  15. toft p, nielsen hk, severinsen i, Helbo-Hanson HS (2024) Effect of epidurally administered bupivacaine on atracurium-induced neuromuscular blockade https://pubmed.ncbi.nlm.nih.gov/2275325/
  16. (2023) "Product Information. Cisatracurium Besylate (cisatracurium)." Hikma Pharmaceuticals USA Inc.
View all 16 references

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Moderate

succinylcholine magnesium sulfate

Applies to: Quelicin (succinylcholine) and adenosine / lidocaine / magnesium sulfate

MONITOR: Magnesium salts may enhance the effects of nondepolarizing neuromuscular blocking agents. One study showed a 25% increase in vecuronium potency after intravenous administration of 40 mg/kg of magnesium sulfate.

MANAGEMENT: Patients should be closely monitored for excessive or prolonged neuromuscular blockade and ventilatory support should be immediately available.

References

  1. (2001) "Product Information. Norcuron (vecuronium)." Organon
  2. Fuchs-Buder T, Wilder-Smith OH, Borgeat A, Tassonyi E (1995) "Interaction of magnesium sulphate with vecuronium-induced neuromuscular block." Br J Anaesth, 74, p. 405-9

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Drug and food interactions

Moderate

lidocaine food

Applies to: adenosine / lidocaine / magnesium sulfate

MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of lidocaine, which is primarily metabolized by the CYP450 3A4 and 1A2 isoenzymes to active metabolites (monoethylglycinexylidide (MEGX) and glycinexylidide). 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. The interaction has not been studied with grapefruit juice but has been reported with oral and/or intravenous lidocaine and potent CYP450 3A4 inhibitor, itraconazole, as well as moderate CYP450 3A4 inhibitor, erythromycin. A pharmacokinetic study of 9 healthy volunteers showed that the administration of lidocaine oral (1 mg/kg single dose) with itraconazole (200 mg daily) increased lidocaine systemic exposure (AUC) and peak plasma concentration (Cmax) by 75% and 55%, respectively. However, no changes were observed in the pharmacokinetics of the active metabolite MEGX. In the same study, when the moderate CYP450 3A4 inhibitor erythromycin (500 mg three times a day) was administered, lidocaine AUC and Cmax increased by 60% and 40%, respectively. By contrast, when intravenous lidocaine (1.5 mg/kg infusion over 60 minutes) was administered on the fourth day of treatment with itraconazole (200 mg once a day) no changes in lidocaine AUC or Cmax were observed. However, when lidocaine (1.5 mg/kg infusion over 60 minutes) was coadministered with erythromycin (500 mg three times a day) in the same study, the AUC and Cmax of the active metabolite MEGX significantly increased by 45-60% and 40%, respectively. The observed differences between oral and intravenous lidocaine when coadministered with CYP450 3A4 inhibitors may be attributed to inhibition of CYP450 3A4 in both the gastrointestinal tract and liver affecting oral lidocaine to a greater extent than intravenous lidocaine. In general, the effects of grapefruit products are concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (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. While the clinical significance of this interaction is unknown, increased exposure to lidocaine may lead to serious and/or life-threatening reactions including respiratory depression, convulsions, bradycardia, hypotension, arrhythmias, and cardiovascular collapse.

MONITOR: Certain foods and behaviors that induce CYP450 1A2 may reduce the plasma concentrations of lidocaine. The proposed mechanism is induction of hepatic CYP450 1A2, one of the isoenzymes responsible for the metabolic clearance of lidocaine. Cigarette smoking is known to be a CYP450 1A2 inducer. In one pharmacokinetic study of 4 smokers and 5 non-smokers who received 2 doses of lidocaine (100 mg IV followed by 100 mg orally after a 2-day washout period), the smokers' systemic exposure (AUC) of oral lidocaine was 68% lower than non-smokers. The AUC of IV lidocaine was only 9% lower in smokers compared with non-smokers. Other CYP450 1A2 inducers include cruciferous vegetables (e.g., broccoli, brussels sprouts) and char-grilled meat. Therefore, eating large or variable amounts of these foods could also reduce lidocaine exposure. The clinical impact of smoking and/or the ingestion of foods that induce CYP450 1A2 on lidocaine have not been studied, however, a loss of efficacy may occur.

MANAGEMENT: Caution is recommended if lidocaine is to be used in combination with grapefruit and grapefruit juice. Monitoring for lidocaine toxicity and plasma lidocaine levels may also be advised, and the lidocaine dosage adjusted as necessary. Patients who smoke and/or consume cruciferous vegetables may be monitored for reduced lidocaine efficacy.

References

  1. Huet PM, LeLorier J (1980) "Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics" Clin Pharmacol Ther, 28, p. 208-15
  2. (2024) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Inc.
  3. (2015) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hospira Healthcare Corporation
  4. (2022) "Product Information. Lidocaine Hydrochloride (lidocaine)." Hameln Pharma Ltd
  5. (2022) "Product Information. Xylocaine HCl (lidocaine)." Aspen Pharmacare Australia Pty Ltd
  6. Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of oral lignocaine https://pubmed.ncbi.nlm.nih.gov/10193676/
  7. Isohanni MH, Neuvonen PJ, Olkkola KT (2024) Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lignocaine https://pubmed.ncbi.nlm.nih.gov/9832299/
View all 7 references

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Moderate

adenosine food

Applies to: adenosine / lidocaine / magnesium sulfate

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

adenosine food

Applies to: adenosine / lidocaine / magnesium sulfate

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: adenosine / lidocaine / magnesium sulfate

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.


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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.