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Drug Interactions between Ionsys and prasugrel

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

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Interactions between your drugs

Moderate

fentaNYL prasugrel

Applies to: Ionsys (fentanyl) and prasugrel

MONITOR: Coadministration with opioid agonists may delay and reduce the absorption of orally administered P2Y12 inhibitors (e.g., clopidogrel, prasugrel, ticagrelor). The proposed mechanism may involve opioid-mediated slowed gastric emptying. In one study, IV morphine (5 mg) given immediately prior to a loading dose of clopidogrel (600 mg) decreased the systemic exposure (AUC) and maximum concentration (Cmax) of the active metabolite of clopidogrel by 34% and increased the time to peak concentration (Tmax) of clopidogrel when compared with placebo (105 minutes vs 83 minutes, respectively). In addition, morphine reduced the pharmacodynamic (antiplatelet) effects of clopidogrel. In another study, IV morphine (5 mg) given immediately prior to a loading dose of ticagrelor (180 mg) decreased the AUC of ticagrelor and its active metabolite by approximately 36%, doubled the Tmax of ticagrelor, and reduced the antiplatelet effects of ticagrelor. The clinical relevance of this interaction is unknown. The risks associated with other opioid agonists are also unknown.

MANAGEMENT: Although data are limited, caution is recommended when orally administered P2Y12 inhibitors are given concomitantly with opioid agonists. In acute coronary syndrome patients who require an opioid agonist, the use of a parenteral antiplatelet agent, such as cangrelor, should be considered.

References

  1. (2001) "Product Information. Plavix (clopidogrel)." Bristol-Myers Squibb
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  5. (2009) "Product Information. Effient (prasugrel)." Lilly, Eli and Company
  6. (2011) "Product Information. Brilinta (ticagrelor)." Astra-Zeneca Pharmaceuticals
  7. Hobl EL, Stimpfl T, Ebner J, et al. (2013) "Morphine Decreases Clopidogrel Concentrations and Effects: A Randomized, Double Blind, Placebo-Controlled Trial." J Am Coll Cardiol
  8. Cerner Multum, Inc. (2015) "Canadian Product Information."
  9. Hobl EL, Reiter B, Schoergenhofer C, et al. (2015) "Morphine Decreases Ticagrelor Concentrations but not its Antiplatelet Effects: A Randomized Trial in Healthy Volunteers." Eur J Clin Invest, 46, p. 7-14
  10. Hobl EL, Reiter B, Schoergenhofer C, et al. (2015) "Morphine interaction with prasugrel: a double-blind, cross-over trial in healthy volunteers." Clin Res Cardiol, 105, p. 349-55
  11. Kubica J, Adamski P, Ostrowska M, et al. (2015) "Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial." Eur Heart J
  12. Kubica J, Kubica A, Jilma B, et al. (2016) "Impact of morphine on antiplatelet effects of oral P2Y12 receptor inhibitors." Int J Cardiol, 215, p. 201-208
View all 12 references

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Drug and food interactions

Major

fentaNYL food

Applies to: Ionsys (fentanyl)

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

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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