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Drug Interactions between lurasidone and MLK F2

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

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Interactions between your drugs

Major

lidocaine BUPivacaine

Applies to: MLK F2 (bupivacaine / lidocaine / triamcinolone) and MLK F2 (bupivacaine / lidocaine / triamcinolone)

GENERALLY AVOID: Additive toxicities may occur when bupivacaine 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: Additional use of local anesthetics should generally be avoided within 96 hours following administration of bupivacaine. If coadministration cannot be avoided, overall local anesthetic exposure through 72 hours must be considered in addition to monitoring for the development of methemoglobinemia as well as central nervous system and cardiovascular adverse reactions. Signs and symptoms of methemoglobinemia may be delayed some hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia such as slate-grey cyanosis in buccal mucous membranes, lips, and nail beds; nausea; headache; dizziness; lightheadedness; lethargy; fatigue; dyspnea; tachypnea; tachycardia; palpitation; anxiety; and confusion. In severe cases, patients may progress to central nervous system depression, stupor, seizures, acidosis, cardiac arrhythmias, syncope, shock, coma, and death. 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 may 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. Cerner Multum, Inc. "Australian Product Information."
  3. (2021) "Product Information. Zynrelef (bupivacaine-meloxicam)." Heron Therapeutics

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Moderate

lidocaine lurasidone

Applies to: MLK F2 (bupivacaine / lidocaine / triamcinolone) and lurasidone

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References

  1. Hamilton MJ, Bush M, Smith P, Peck AW (1982) "The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man." Br J Clin Pharmacol, 14, p. 791-7
  2. Stambaugh JE, Lane C (1983) "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest, 1, p. 111-7
  3. Sotaniemi EA, Anttila M, Rautio A, et al. (1981) "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther, 29, p. 705-10
  4. Grabowski BS, Cady WJ, Young WW, Emery JF (1980) "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol, 18, p. 317-9
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF (1988) "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther, 43, p. 412-9
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  8. Naylor GJ, McHarg A (1977) "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J, 2, p. 22
  9. Stovner J, Endresen R (1965) "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand, 24, p. 223-7
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF (1984) "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol, 36, p. 244-7
  11. Feldman SA, Crawley BE (1970) "Interaction of diazepam with the muscle-relaxant drugs." Br Med J, 1, p. 336-8
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF (1988) "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl), 96, p. 63-6
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I (1989) "Midazolam-morphine sedative interaction in patients." Anesth Analg, 68, p. 282-5
  15. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
  16. Greiff JMC, Rowbotham D (1994) "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet, 27, p. 447-61
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G (1989) "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand, 80 Suppl, p. 95-8
  18. Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
  19. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
  20. (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
  21. (2001) "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc)
  22. (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
  23. (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
  24. (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
  25. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  26. (2001) "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical
  27. (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
  28. Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
  29. Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
  30. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
  31. (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
  32. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  33. Cerner Multum, Inc. "Australian Product Information."
  34. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  35. (2014) "Product Information. Belsomra (suvorexant)." Merck & Co., Inc
  36. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
View all 36 references

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Drug and food interactions

Major

lurasidone food

Applies to: lurasidone

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of lurasidone. 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 for other CYP450 3A4 inhibitors. When a single 10 mg dose of lurasidone was administered with the potent CYP450 3A4 inhibitor ketoconazole (400 mg/day for 5 days), lurasidone peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 6.9- and 9.0-fold, respectively, compared to administration alone. The AUC of lurasidone's active metabolite increased by 6-fold. Another potent CYP450 3A4 inhibitor, posaconazole, has been reported to increase lurasidone AUC by approximately 4.5-fold. When a single 20 mg dose of lurasidone was administered with the moderate CYP450 3A4 inhibitor diltiazem (extended release formulation 240 mg/day for 5 days), lurasidone Cmax and AUC increased by 2.1- and 2.2-fold, respectively, while the AUC of the active metabolite increased by 2.4-fold. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (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.

GENERALLY AVOID: Alcohol may potentiate some of the central nervous system and hypotensive effects of lurasidone. Use in combination may result in increased sedation, dizziness, hypotension, and impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of lurasidone. According to the product labeling, lurasidone mean Cmax and AUC were increased approximately 3-fold and 2-fold, respectively, when administered with food relative to under fasting conditions. Lurasidone AUC was not affected by meal size (in the range of 350 to 1000 calories) or fat content. In clinical studies, lurasidone was administered with food.

MANAGEMENT: Patients treated with lurasidone should avoid consumption of grapefruit and grapefruit juice as well as alcohol. Lurasidone should be taken with food (at least 350 calories).

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  3. Cerner Multum, Inc. "Australian Product Information."
  4. (2010) "Product Information. Latuda (lurasidone)." Sunovion Pharmaceuticals Inc
View all 4 references

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Moderate

lidocaine food

Applies to: MLK F2 (bupivacaine / lidocaine / triamcinolone)

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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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.