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Drug Interactions between Fentanyl Transdermal System and Suprenza

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

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Interactions between your drugs

Moderate

fentaNYL phentermine

Applies to: Fentanyl Transdermal System (fentanyl) and Suprenza (phentermine)

MONITOR: Coadministration of amphetamines and amphetamine-like drugs with certain opioids or the synthetic opioid derivative, dextromethorphan, may increase the risk of serotonin syndrome. Dextromethorphan and some opioids, particularly those in the phenylpiperidine class, are weak serotonin reuptake inhibitors whose effects may be potentiated by amphetamines. However, clinical data are limited. Case reports of serotonin syndrome involving these agents have primarily been associated with concomitant use of highly serotonergic substances such as selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, monoamine oxidase inhibitors, and other antidepressants. Rarely, except in the case of abuse or overdose, has serotonin syndrome been associated with the use of amphetamines, opioids, or dextromethorphan alone or with each other. In the case of amphetamines, serotonin syndrome has most frequently been reported with the use of MDMA, or ecstasy, an amphetamine derivative with enhanced serotonergic activity over classical amphetamines, which tend to be more dopaminergic. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of 5-HT1A and 2A receptors in the brainstem and peripheral nervous system. Symptoms may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MANAGEMENT: Caution is recommended when amphetamines and amphetamine-like drugs are used with dextromethorphan or opioids with serotonergic effects such as fentanyl, meperidine, methadone, propoxyphene, and tramadol. Patients should be monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures.

References

  1. "Product Information. Desoxyn (methamphetamine)." Abbott Pharmaceutical PROD (2001):
  2. "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc PROD (2001):
  3. "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals PROD (2001):
  4. Gillman PK "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth (2005):
  5. Hunter B, Kleinert MM, Osatnik J, Soria E "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg 102 (2006): 1589
  6. "Product Information. Vyvanse (lisdexamfetamine)." Shire US Inc (2007):
  7. Lee J, Franz L, Goforth HW "Serotonin syndrome in a chronic-pain patient receiving concurrent methadone, ciprofloxacin, and venlafaxine." Psychosomatics 50 (2009): 638-9
  8. "Product Information. Nuedexta (dextromethorphan-quinidine)." Avanir Pharmaceuticals, Inc (2010):
  9. Mugele J, Nanagas KA, Tormoehlen LM "Serotonin Syndrome Associated With MDPV Use: A Case Report." Ann Emerg Med (2012):
  10. Davis JJ, Buck NS, Swenson JD, Johnson KB, Greis PE "Serotonin syndrome manifesting as patient movement during total intravenous anesthesia with propofol and remifentanil." J Clin Anesth 25 (2013): 52-4
  11. "Product Information. Adipex-P (phentermine)." Teva Pharmaceuticals (formerly Gate Pharmaceuticals) (2016):
View all 11 references

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Drug and food interactions

Major

fentaNYL food

Applies to: Fentanyl Transdermal System (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. "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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Moderate

phentermine food

Applies to: Suprenza (phentermine)

GENERALLY AVOID: Alcohol may potentiate the central nervous system and cardiovascular effects of centrally-acting appetite suppressants. In one study, concurrent administration of methamphetamine (30 mg intravenously) and ethanol (1 gm/kg orally over 30 minutes) increased heart rate by 24 beats/minute compared to methamphetamine alone. This increases cardiac work and myocardial oxygen consumption, which may lead to more adverse cardiovascular effects than either agent alone. Subjective effects of ethanol were diminished in the eight study subjects, but those of methamphetamine were not affected. The pharmacokinetics of methamphetamine were also unaffected except for a decrease in the apparent volume of distribution at steady state.

MANAGEMENT: Concomitant use of centrally-acting appetite suppressants and alcohol should be avoided if possible, especially in patients with a history of cardiovascular disease. Patients should be counselled to avoid hazardous activities requiring complete 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. Mendelson J, Jones RT, Upton R, Jacob P 3rd "Methamphetamine and ethanol interactions in humans." Clin Pharmacol Ther 57 (1995): 559-68
  2. "Product Information. Didrex (benzphetamine)." Pharmacia and Upjohn PROD (2001):
  3. "Product Information. Suprenza (phentermine)." Akrimax Pharmaceuticals (2012):

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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.