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Drug Interaction Report

7 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Major

azithromycin morphine

Applies to: azithromycin / trovafloxacin, Embeda (morphine / naltrexone)

MONITOR CLOSELY: Coadministration with P-glycoprotein (P-gp) inhibitors may increase the plasma concentrations of morphine and its risk of adverse effects, including hypotension, respiratory and CNS depression, profound sedation, coma, and death. The proposed mechanism may involve inhibition of the intestinal P-gp efflux transporter, resulting in enhanced oral bioavailability of morphine, a P-gp substrate. The interaction may be more significant for orally administered morphine. According to some authorities, the concomitant use of a P-gp inhibitor with oral morphine may increase the systemic exposure of morphine by approximately 2-fold. However, in a pharmacokinetic study involving 12 healthy subjects, itraconazole (200 mg daily for 4 days), a strong P-gp inhibitor, increased the morphine (0.3 mg/kg as a single oral dose) peak plasma concentration (Cmax) and systemic exposure (AUC) by 28% and 22%, respectively. Plasma concentrations of intravenously administered morphine appear less affected. In a crossover study involving 14 healthy volunteers, intravenous administration of P-gp inhibitor cyclosporine followed by an intravenous infusion of morphine 0.1 mg/kg led to a minimal increase of morphine AUC to 100 ng/mL*h compared to 85 ng/mL*h when administered after control (no infusion). In the same study, cyclosporine appeared to prolong morphine-induced miosis.

MANAGEMENT: Caution is recommended whenever morphine, particularly orally administered morphine, is used concomitantly with a P-gp inhibitor. Close clinical and laboratory monitoring should be considered whenever a P-gp inhibitor is added to or withdrawn from therapy, and the morphine dosage adjusted as necessary. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation that may be greater than otherwise expected. In addition, patients should be advised to avoid driving or operating hazardous machinery until they know how these medications affect them.

References

  1. (2002) "Product Information. MS Contin (morphine)." Purdue Frederick Company
  2. (2001) "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals
  3. Kharasch ED, Hoffer C, Whittington D, Sheffels P (2003) "Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine." Clin Pharmacol Ther, 74, p. 543-54
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Cerner Multum, Inc. "Australian Product Information."
  6. Meissner K, Avram MJ, Yermolenka V, Francis AM, Blood J, Kharasch ED (2013) "Cyclosporine-inhibitable Blood-Brain Barrier Drug Transport Influences Clinical Morphine Pharmacodynamics." Anesthesiology
  7. Heiskanen T, Backman JT, Neuvonen M, Kontinen VK, Neuvonen PJ, Kalso E (2008) "Itraconazole, a potent inhibitor of P-glycoprotein, moderately increases plasma concentrations of oral morphine." Acta Anaesthesiol Scand, 52, p. 1319-26
View all 7 references

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Major

morphine naltrexone

Applies to: Embeda (morphine / naltrexone), Embeda (morphine / naltrexone)

CONTRAINDICATED: Naltrexone can antagonize the effects of opioids via competitive inhibition of opioid receptors. Patients receiving naltrexone may not benefit from opioid-containing medications such as cough and cold products, antidiarrheal preparations, and narcotic analgesics. Likewise, patients dependent on opioids may experience withdrawal symptoms when given naltrexone. Following use of naltrexone, patients may have increased sensitivity to opioids.

**Note: This warning does not apply to opioid products that are specifically formulated with naltrexone to deter abuse via snorting or intravenous injection when crushed.**

MANAGEMENT: The use of naltrexone is considered contraindicated in patients receiving opioids or dependent on opioids, including those maintained on opiate agonists (e.g., methadone) or partial agonists (e.g., buprenorphine). Naltrexone should also not be given to patients in acute opioid withdrawal. In an urgent situation when analgesia may be required in a patient who has received full blocking doses of naltrexone, consideration should be given to regional analgesia, conscious sedation with a benzodiazepine, use of non-opioid analgesics, or general anesthesia. If opioid analgesia is required, the amount of opioid needed may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged. A rapidly-acting opioid analgesic that minimizes the duration of respiratory depression is preferred. Clinicians should be aware that reversal of full naltrexone blockade by administration of large doses of opiates can cause histamine release. Therefore, patients may experience non-opioid receptor-mediated effects such as facial swelling, itching, generalized erythema, and bronchoconstriction. Irrespective of the drug chosen to reverse naltrexone blockade, the patient should be monitored closely by appropriately trained personnel in a setting equipped and staffed for cardiopulmonary resuscitation.

References

  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals

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Moderate

azithromycin naltrexone

Applies to: azithromycin / trovafloxacin, Embeda (morphine / naltrexone)

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Periodic monitoring of hepatic function is advisable.

References

  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals

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Moderate

morphine trovafloxacin

Applies to: Embeda (morphine / naltrexone), azithromycin / trovafloxacin

ADJUST DOSING INTERVAL: Coadministration of oral trovafloxacin with intravenous morphine significantly decreases the absorption of trovafloxacin. Loss of efficacy may result. The mechanism of the interaction is not known.

MANAGEMENT: If these drugs must be coadministered, intravenous morphine should be administered at least two hours after the oral trovafloxacin dose in the fasted state and at least four hours after oral trovafloxacin in the fed state.

References

  1. (2001) "Product Information. Trovan (trovafloxacin)." Pfizer U.S. Pharmaceuticals
  2. Vincent J, Hunt T, Teng RL, Robarge L, Willavize SA, Friedman HL (1998) "The pharmacokinetic effects of coadministration of morphine and trovafloxacin in healthy subjects." Am J Surg, 176, s32-8

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Moderate

naltrexone trovafloxacin

Applies to: Embeda (morphine / naltrexone), azithromycin / trovafloxacin

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Periodic monitoring of hepatic function is advisable.

References

  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals

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Drug and food interactions

Major

morphine food

Applies to: Embeda (morphine / naltrexone)

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including morphine and diamorphine. 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 morphine may cause rapid release of the drug, resulting in high systemic levels of morphine that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. The interaction was observed in in vitro studies using a 24-hour morphine formulation (Avinza 30 mg capsule, available in the U.S. from Ligand Pharmaceuticals). When the capsule was mixed with 900 mL of buffer solutions containing ethanol 20% and 40%, the dose of morphine that was released was alcohol concentration-dependent, leading to a more rapid release of morphine. Although the clinical relevance of this finding is unknown, 'dose-dumping' into the bloodstream is conceivable.

MANAGEMENT: Until more information is available, patients taking sustained-release formulations of morphine should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as morphine or diamorphine should not be combined with alcohol.

References

  1. (2005) "Product Information. Avinza (morphine)." Ligand Pharmaceuticals
  2. Ghalie R (2005) Dear Health Care Professional. http://www.fda.gov/medwatch/safety/2005/AVINZA_DHCP_Letter_Oct2005.pdf
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. (2015) "Canadian Product Information."
View all 4 references

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Moderate

naltrexone food

Applies to: Embeda (morphine / naltrexone)

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice). Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Periodic monitoring of hepatic function is advisable.

References

  1. (2001) "Product Information. ReVia (naltrexone)." DuPont Pharmaceuticals

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Therapeutic duplication warnings

No duplication 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.

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Further information

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