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Drug Interactions between fentanyl / ropivacaine and Urelief Plus

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

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Interactions between your drugs

Major

fentaNYL butabarbital

Applies to: fentanyl / ropivacaine and Urelief Plus (butabarbital / hyoscyamine / phenazopyridine)

GENERALLY AVOID: Barbiturates may potentiate the central nervous system (CNS) depressant effects of opioids. Concomitant use may result in profound sedation, respiratory depression, coma, and death. On the other hand, some barbiturates can also induce the hepatic metabolism of opioids that are metabolized by CYP450 3A4 such as butorphanol, fentanyl, hydrocodone, methadone and oxycodone, resulting in enhanced clearance. Reduced analgesic efficacy or withdrawal symptoms may occur in patients maintained on their opioid regimen following the addition of a barbiturate. Conversely, discontinuation of the barbiturate may increase plasma concentrations of the opioid and potentiate the risk of overdose and fatal respiratory depression.

MANAGEMENT: The use of opioids in conjunction with other CNS depressants such as barbiturates should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, and patients should be closely monitored for signs and symptoms of CNS and respiratory depression. Particular caution is advisable when a barbiturate is added to or withdrawn from therapy in patients receiving opioids that are CYP450 3A4 substrates, as there may be an increased risk of withdrawal symptoms (e.g., restlessness, insomnia, sweating, lacrimation, or rhinorrhea) following initiation of the barbiturate and overdose following discontinuation. A dosage adjustment for one or both drugs may be required.

References

  1. Liu S-J, Wang RI "Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome." Am J Psychiatry 141 (1984): 1287-8
  2. Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9
  3. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  4. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical (2006):
  7. Cerner Multum, Inc. "Australian Product Information." O 0
  8. "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc (2013):
  9. "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation (2017):
  10. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 10 references

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Moderate

fentaNYL hyoscyamine

Applies to: fentanyl / ropivacaine and Urelief Plus (butabarbital / hyoscyamine / phenazopyridine)

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. 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. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  2. "Product Information. Dolophine (methadone)." Lilly, Eli and Company PROD (2002):
  3. "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals PROD (2001):
  4. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  5. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  6. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  7. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  8. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  10. "Product Information. Opana (oxymorphone)." Endo Laboratories LLC (2006):
  11. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  12. "Product Information. Exalgo (hydromorphone)." Covidien (2010):
  13. "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc (2016):
  14. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  15. "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc (2017):
  16. "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc (2017):
  17. "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics (2017):
  18. "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc) (2018):
  19. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 19 references

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Moderate

phenazopyridine ROPivacaine

Applies to: Urelief Plus (butabarbital / hyoscyamine / phenazopyridine) and fentanyl / ropivacaine

MONITOR: Coadministration of local anesthetics with other oxidizing agents that can also induce methemoglobinemia such as antimalarials (e.g., chloroquine, quinine), nitrates and nitrites, sulfonamides, aminosalicylic acid, dimethyl sulfoxide (DMSO), metoclopramide, nitrofurantoin, phenazopyridine, phenobarbital, and phenytoin may increase the risk. Additional risk factors include very young age (e.g., infants less than 6 months), cardiac or pulmonary disease, genetic predisposition, and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Data surrounding the incidence of methemoglobinemia are agent-specific and, in many instances, have primarily been reported in case reports and/or in overdose situations.

MANAGEMENT: Monitoring for signs and symptoms of methemoglobinemia is recommended if local anesthetics must be used with other methemoglobin-inducing agents. Signs and symptoms of methemoglobinemia may occur immediately or hours after drug exposure. Patients or their caregivers should be advised to seek medical attention if they notice signs and symptoms of methemoglobinemia (e.g., cyanotic skin discoloration, abnormal blood coloration, 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. Methemoglobinemia should be considered if central cyanosis is unresponsive to oxygen. Calculated oxygen saturation and pulse oximetry are generally not accurate in the setting of methemoglobinemia. The diagnosis can be confirmed by an elevated methemoglobin level of at least 10% using co-oximetry. Methemoglobin concentrations greater than 10% of total hemoglobin will typically cause cyanosis, and levels over 70% are frequently fatal. However, symptom severity is not always related to methemoglobin levels. Experts suggest that treatment of methemoglobinemia varies from supplemental oxygen and symptom support to the administration of methylene blue, depending on severity of symptoms and/or the presence of G6PD deficiency. Institutional guidelines and/or individual product labeling should be consulted for further guidance.

References

  1. "Product Information. Marcaine HCl (bupivacaine)." Hospira Inc (2008):
  2. Guay J "Methemoglobinemia related to local anesthetics: a summary of 242 episodes." Anesth Analg 108 (2009): 837-45
  3. Skold A, Cosco DL, Klein R "Methemoglobinemia: pathogenesis, diagnosis, and management." South Med J 104 (2011): 757-61
  4. "Product Information. Zynrelef (bupivacaine-meloxicam)." Heron Therapeutics (2021):
View all 4 references

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Drug and food interactions

Major

fentaNYL food

Applies to: fentanyl / ropivacaine

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. "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical PROD (2001):
  3. Kharasch ED, Whittington D, Hoffer C "Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate." Anesthesiology 101 (2004): 729-737
  4. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg 82 (1996): 167-72
  5. Labroo RB, Paine MF, Thummel KE, Kharasch ED "Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implicaitons for interindividual variability in disposition, efficacy, and drug interactions." Drug Metab Dispos 25 (1997): 1072-80
View all 5 references

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Major

butabarbital food

Applies to: Urelief Plus (butabarbital / hyoscyamine / phenazopyridine)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

hyoscyamine food

Applies to: Urelief Plus (butabarbital / hyoscyamine / phenazopyridine)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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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.