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Drug Interactions between eluxadoline and meperidine / promethazine

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

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Interactions between your drugs

Moderate

meperidine promethazine

Applies to: meperidine / promethazine and meperidine / promethazine

ADJUST DOSE: The central nervous system and respiratory depressant effects of meperidine may be potentiated by concomitant use of other agents with CNS depressant effects. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered, particularly in elderly or debilitated patients.

MANAGEMENT: Caution and dosage adjustments are advisable when meperidine is used in combination with other narcotic analgesics, general anesthetics, phenothiazines, sedative-hypnotics, tranquilizers, tricyclic antidepressants, or other CNS depressants such as alcohol. A lower dosage of meperidine should be considered initially, then titrated carefully according to pain level and clinical response. Meperidine dosage reductions of 25% to 50% have been recommended for patients receiving phenothiazines and other tranquilizers. Patients should be advised to avoid rising abruptly from a sitting or recumbent position, and to notify their physician if they experience dizziness, lightheadedness, orthostasis, syncope, tachycardia, or excessive CNS effects that interfere with their normal activities. Patients should also avoid driving or operating hazardous machinery until they know how these medications affect them.

References

  1. Lambertsen CJ, Wendel H, Longenhagen JB "The separate and combined respiratory effects of chlorpromazine and meperidine in normal men controlled at 46 mm Hg alveolar pCO2." J Pharmacol Exp Ther 131 (1961): 381-93
  2. Hoffman JC, Smith TC "The respiratory effects of meperidine and propiomazine in man." Anesthesiology 32 (1970): 325-31
  3. Stambaugh JE, Wainer IW "Drug interaction: meperidine and chlorpromazine, a toxic combination." J Clin Pharmacol 21 (1981): 140-6
  4. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  5. "Product Information. Meperidine Hydrochloride (meperidine)." Astra-Zeneca Pharmaceuticals (2022):
View all 5 references

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Moderate

meperidine eluxadoline

Applies to: meperidine / promethazine and eluxadoline

GENERALLY AVOID: The risk of constipation and serious constipation-related adverse reactions may be increased when eluxadoline is used with other drugs that are also associated with this adverse effect. In placebo-controlled studies, constipation occurred in 7% and 8% of patients receiving eluxadoline 75 mg twice daily and 100 mg twice daily, respectively. Approximately 50% of constipation events occurred within the first 2 weeks of treatment, while the majority occurred within the first 3 months. The rates of constipation were similar between eluxadoline and placebo beyond the first 3 months of therapy.

MANAGEMENT: Concomitant use of eluxadoline with other drugs that can cause constipation such as alosetron, anticholinergics, and opioids should generally be avoided. Loperamide may be used occasionally for acute management of severe diarrhea, but chronic use is not recommended, and it should be discontinued immediately if constipation occurs. Eluxadoline should also be discontinued if constipation occurs for more than 4 days.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Viberzi (eluxadoline)." Actavis Pharma, Inc. (2015):

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Moderate

promethazine eluxadoline

Applies to: meperidine / promethazine and eluxadoline

GENERALLY AVOID: The risk of constipation and serious constipation-related adverse reactions may be increased when eluxadoline is used with other drugs that are also associated with this adverse effect. In placebo-controlled studies, constipation occurred in 7% and 8% of patients receiving eluxadoline 75 mg twice daily and 100 mg twice daily, respectively. Approximately 50% of constipation events occurred within the first 2 weeks of treatment, while the majority occurred within the first 3 months. The rates of constipation were similar between eluxadoline and placebo beyond the first 3 months of therapy.

MANAGEMENT: Concomitant use of eluxadoline with other drugs that can cause constipation such as alosetron, anticholinergics, and opioids should generally be avoided. Loperamide may be used occasionally for acute management of severe diarrhea, but chronic use is not recommended, and it should be discontinued immediately if constipation occurs. Eluxadoline should also be discontinued if constipation occurs for more than 4 days.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. "Product Information. Viberzi (eluxadoline)." Actavis Pharma, Inc. (2015):

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Drug and food interactions

Major

eluxadoline food

Applies to: eluxadoline

CONTRAINDICATED: Consumption of more than 3 alcoholic beverages per day may increase the risk of acute pancreatitis during treatment with eluxadoline. Pancreatitis has been reported rarely during clinical trials of eluxadoline, and may or may not be related to sphincter of Oddi spasm.

ADJUST DOSING INTERVAL: High-fat meals may reduce the oral bioavailability of eluxadoline. In 28 healthy volunteers, administration of a single 100 mg dose of eluxadoline with a high-fat meal (approximately 800 to 1000 total calories, 50% from fat) decreased eluxadoline peak plasma concentration (Cmax) and systemic exposure (AUC) by 50% and 60%, respectively, compared to administration in the fasted state. There was no significant effect on the time to peak concentration (Tmax). The clinical relevance of this interaction is unknown. It should be noted that phase 3 clinical trials were conducted under fed conditions.

MANAGEMENT: Chronic or acute excessive use of alcohol should be avoided during treatment with eluxadoline. Alcoholism, alcohol abuse, alcohol addiction, and consumption of more than 3 alcoholic beverages per day are considered contraindications to the use of eluxadoline. The product labeling recommends taking eluxadoline with food. Patients should be advised to stop taking eluxadoline and seek medical attention if they experience potential symptoms of pancreatitis such as persistent nausea, vomiting, abdominal tenderness, and upper abdominal pain, especially that which is made worse after eating or radiates to the back or shoulders.

References

  1. "Product Information. Viberzi (eluxadoline)." Actavis Pharma, Inc. (2015):

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Moderate

meperidine food

Applies to: meperidine / promethazine

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. 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.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther 15 (1974): 368-73
  2. Sturner WQ, Garriott JC "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA 223 (1973): 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol 41 (1991): 147-52
  4. Levine B, Saady J, Fierro M, Valentour J "A hydromorphone and ethanol fatality." J Forensic Sci 29 (1984): 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol 19 (1985): 398-401
  6. Carson DJ "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet 1 (1977): 894-7
  7. Rosser WW "The interaction of propoxyphene with other drugs." Can Med Assoc J 122 (1980): 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM "Distalgesic and ethanol-impaired function." Lancet 2 (1982): 384
  9. Kiplinger GF, Sokol G, Rodda BE "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther 212 (1974): 175-80
View all 9 references

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Moderate

promethazine food

Applies to: meperidine / promethazine

GENERALLY AVOID: Concurrent use of ethanol and phenothiazines may result in additive CNS depression and psychomotor impairment. Also, ethanol may precipitate dystonic reactions in patients who are taking phenothiazines. The two drugs probably act on different sites in the brain, although the exact mechanism of the interaction is not known.

MANAGEMENT: Patients should be advised to avoid alcohol during phenothiazine therapy.

References

  1. Lutz EG "Neuroleptic-induced akathisia and dystonia triggered by alcohol." JAMA 236 (1976): 2422-3
  2. Freed E "Alcohol-triggered-neuroleptic-induced tremor, rigidity and dystonia." Med J Aust 2 (1981): 44-5

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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

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