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Drug Interactions between clopidogrel and Entuss-D JR

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

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Interactions between your drugs

Moderate

HYDROcodone clopidogrel

Applies to: Entuss-D JR (guaifenesin / hydrocodone / pseudoephedrine) and clopidogrel

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

HYDROcodone food

Applies to: Entuss-D JR (guaifenesin / hydrocodone / pseudoephedrine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. 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 alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.

MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.

References

  1. (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc

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Moderate

pseudoephedrine food

Applies to: Entuss-D JR (guaifenesin / hydrocodone / pseudoephedrine)

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 (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
  2. Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
  3. (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
  4. (2001) "Product Information. Tenuate (diethylpropion)." Aventis Pharmaceuticals
  5. (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
  6. (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
  7. (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
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.

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