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Drug Interactions between bupivacaine liposome and fentanyl / ropivacaine

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

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Interactions between your drugs

Major

ROPivacaine BUPivacaine liposome

Applies to: fentanyl / ropivacaine and bupivacaine liposome

ADJUST DOSING INTERVAL: Administration of bupivacaine liposome suspension together with other local anesthetics, either simultaneously in the same syringe or sequentially to the same site, may impact the pharmacokinetic and/or physicochemical properties of bupivacaine liposome. In vitro and animal studies have shown that local anesthetics such as lidocaine, mepivacaine, and ropivacaine can cause substantial displacement and rapid release of free bupivacaine from liposomes, which may affect the safety and efficacy of the medication.

MONITOR CLOSELY: Additive toxicities may occur when bupivacaine liposome suspension is coadministered with other local anesthetics. The potential for increased risk of systemic toxicities such as methemoglobinemia and central nervous system and cardiovascular adverse reactions should be recognized.

MANAGEMENT: Bupivacaine liposome suspension should not be admixed with other, non-bupivacaine based local anesthetics. It may be admixed with bupivacaine hydrochloride as long as the ratio of the milligram dose of bupivacaine HCl to bupivacaine liposome does not exceed 1:2. Additional use of local anesthetics should generally be avoided within 96 hours following administration of bupivacaine liposome suspension. According to the manufacturer, bupivacaine liposome may be locally administered after at least 20 minutes following the local administration of lidocaine. However, there are 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, caution and close observation for development of methemoglobinemia as well as central nervous system and cardiovascular adverse reactions are advised during concomitant use. Early warning signs of central nervous system toxicity may include restlessness, anxiety, incoherent speech, dizziness, lightheadedness, numbness and tingling of the mouth and lips, metallic taste, tinnitus, blurred vision, tremors, twitching, depression, and drowsiness. Cardiovascular toxicity include atrioventricular block, ventricular arrhythmias, cardiac arrest, and decreased cardiac output and arterial blood pressure due to depressed cardiac conductivity, excitability, and myocardial contractility. Patients should have cardiovascular and respiratory vital signs and state of consciousness constantly monitored while under treatment.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2011) "Product Information. Exparel (BUPivacaine liposome)." Pacira Pharmaceuticals Inc
  3. Kharitonov V (2014) "A review of the compatibility of liposome bupivacaine with other drug products and commonly used implant materials." Postgrad Med, 126, p. 129-38

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Drug and food interactions

Major

fentaNYL food

Applies to: fentanyl / ropivacaine

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including fentanyl. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Consumption of grapefruit juice during treatment with oral transmucosal formulations of fentanyl may result in increased plasma concentrations of fentanyl, which is primarily metabolized by CYP450 3A4 isoenzyme in the liver and intestine. Certain compounds present in grapefruit are known to inhibit CYP450 3A4 and may increase the bioavailability of swallowed fentanyl (reportedly up to 75% of a dose) and/or decrease its systemic clearance. The clinical significance is unknown. In 12 healthy volunteers, consumption of 250 mL regular-strength grapefruit juice the night before and 100 mL double-strength grapefruit juice one hour before administration of oral transmucosal fentanyl citrate (600 or 800 mcg lozenge) did not significantly affect fentanyl pharmacokinetics, overall extent of fentanyl-induced miosis (miosis AUC), or subjective self-assessment of various clinical effects compared to control. However, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with fentanyl. Any history of alcohol or illicit drug use should be considered when prescribing fentanyl, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with fentanyl should preferably avoid the consumption of grapefruit and grapefruit juice. In addition, patients receiving transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.

References

  1. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  2. (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
  3. Kharasch ED, Whittington D, Hoffer C (2004) "Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate." Anesthesiology, 101, p. 729-737
  4. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M (1996) "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg, 82, p. 167-72
  5. Labroo RB, Paine MF, Thummel KE, Kharasch ED (1997) "Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implicaitons for interindividual variability in disposition, efficacy, and drug interactions." Drug Metab Dispos, 25, p. 1072-80
View all 5 references

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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:

  • bupivacaine liposome
  • fentanyl/ropivacaine

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.

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.

Further information

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

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