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Drug Interactions between Exparel and Xylocaine-MPF-Epinephrine

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

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Interactions between your drugs

Major

lidocaine BUPivacaine liposome

Applies to: Xylocaine-MPF-Epinephrine (epinephrine / lidocaine) and Exparel (bupivacaine liposome)

BUPivacaine liposome is a specially formulated anesthetic that releases the medication into the surrounding tissue at a controlled rate. When exposed to other local anesthetic solutions, the release rate can be altered. Therefore, BUPivacaine liposome and lidocaine should not be mixed together or injected into the same area at the same time, as it may cause rapid release of the active medication and alter the safety and efficacy of BUPivacaine liposome. Additional use of local anesthetics including lidocaine should generally be avoided within 96 hours following administration of BUPivacaine liposome. If necessary, BUPivacaine liposome may be locally administered after at least 20 minutes following the local administration of lidocaine. However, there are currently no data to support administration of other local, non-bupivacaine based anesthetics prior to administration of BUPivacaine liposome. Because the toxic effects of these medications are additive, using them together requires caution and constant monitoring of vital signs and state of consciousness to prevent serious and potentially life-threatening side effects such as methemoglobinemia (a condition that can deprive tissues and organs of oxygen), central nervous system reactions (e.G., convulsions, unconsciousness, coma, respiratory arrest), and cardiovascular disorders (e.G., low blood pressure, heart block, irregular heart rhythm, cardiac arrest). Patients require immediate medical attention if they develop signs and symptoms of methemoglobinemia such as pale, gray, or blue colored skin (cyanosis); headache; rapid heart rate; shortness of breath; lightheadedness; or fatigue.

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Drug and food interactions

Moderate

lidocaine food

Applies to: Xylocaine-MPF-Epinephrine (epinephrine / lidocaine)

Consumer information for this interaction is not currently available.

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

EPINEPHrine food

Applies to: Xylocaine-MPF-Epinephrine (epinephrine / lidocaine)

Consumer information for this interaction is not currently available.

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

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Local injectable anesthetics

Therapeutic duplication

The recommended maximum number of medicines in the 'local injectable anesthetics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'local injectable anesthetics' category:

  • Exparel (bupivacaine liposome)
  • Xylocaine-MPF-Epinephrine (epinephrine/lidocaine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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.