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Alfenta and PCE Dispertab

Determining the interaction of Alfenta and PCE Dispertab and the possibility of their joint administration.

Check result:
Alfenta <> PCE Dispertab
Relevance: 28.03.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Erythromycin may significantly increase the blood levels of alfentanil. This can increase the risk and/or severity of side effects such as excessive sedation, respiratory depression, low blood pressure, and irregular heart rhythm. You may need a dose adjustment to safely use both medications. Talk to your doctor if you have any questions or concerns. Your doctor may already be aware of the risks, but has determined that this is the best course of treatment for you and has taken appropriate precautions and is monitoring you closely for any potential complications. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

Professional:

MONITOR CLOSELY: Coadministration with potent and moderate inhibitors of CYP450 3A4 may significantly increase the plasma concentrations of alfentanil, which is primarily metabolized by the isoenzyme. In six healthy volunteers, pretreatment with erythromycin (500 mg twice a day for 7 days) increased the mean elimination half-life of alfentanil (50 mcg/kg single IV dose) from 84 to 131 minutes and decreased its clearance from 3.9 to 2.9 mL/kg/min relative to placebo. The combination was also suspected in association with isolated reports of prolonged sedation and respiratory depression. In nine healthy volunteers, pretreatment with troleandomycin (500 mg orally every 12 hours for 4 doses) resulted in a 79% decrease in the clearance of alfentanil (20 mcg/kg IV bolus dose) compared to control. Another study in twelve healthy subjects found that troleandomycin (500 mg orally 1.7 hours before alfentanil, then 250 mg every 6 hours for 3 more doses) reduced the clearance of alfentanil (15 mcg/kg single IV dose) by 88% and increased its Cmax and AUC by 31% and 83%, respectively, compared to placebo. In 30 patients undergoing coronary artery bypass grafting, the mean half-life of alfentanil (50 mcg/kg for induction and 1 mcg/kg/min for maintenance) was 50% longer and the systemic exposure (AUC) 24% to 40% greater in patients who were coadministered diltiazem (60 mg orally 2 hours before induction of anesthesia and 0.1 mg/kg/hr starting at induction and continued for 23 hours) than in patients who were not. The time for alfentanil plasma level to decrease 50% after cessation of the infusion was also 40% longer in the diltiazem group. Although the time to awakening was not significantly different, the time to extubation was delayed an average of 2.5 hours by diltiazem compared to placebo. In nine healthy volunteers administered alfentanil 20 mcg/kg in three separate phases, alfentanil clearance was 1.3 and 1.4 mL/min/kg following pretreatment (60 minutes before alfentanil) with a single 400 mg IV dose and 400 mg oral dose of fluconazole, respectively, versus 3.1 mL/min/kg following pretreatment with placebo. The mean elimination half-life of alfentanil nearly doubled after both IV and oral fluconazole compared to placebo (2.7 and 2.5 hours vs. 1.5 hours, respectively), and respiratory depression and subjective effects of alfentanil were both increased by fluconazole. In another study consisting of 19 intensive care unit patients, pretreatment with IV cimetidine (1200 mg daily for 48 hours) increased the half-life of alfentanil (125 mcg/kg single IV dose) by 75% and reduced its clearance by 64% compared to an oral aluminum/magnesium hydroxide antacid, whereas IV ranitidine (300 mg daily for 48 hours) had no significant effect.

MANAGEMENT: Lower dosages of alfentanil may be required when used in combination with potent and moderate CYP450 3A4 inhibitors (e.g., azole antifungal agents, protease inhibitors, ketolide and certain macrolide antibiotics, aprepitant, diltiazem, dalfopristin-quinupristin, delavirdine, imatinib, nefazodone, verapamil). Patients should be carefully monitored for excessive central nervous system and respiratory depression, and dosage adjustments made accordingly if necessary. Recovery time from alfentanil anesthesia may be prolonged in some cases.

References
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  • Kharasch ED, Walker A, Hoffer C, Sheffels P "Intravenous and oral alfentanil as in vivo probes for hepatic and first-pass cytochrome P450 3A activity: noninvasive assessment by use of pupillary miosis." Clin Pharmacol Ther 76 (2004): 452-66
  • Ibrahim AE, Feldman J, Karim A, Kharasch ED "Simultaneous Assessment of Drug Interactions with Low- and High-Extraction Opioids: Application to Parecoxib Effects on the Pharmacokinetics and Pharmacodynamics of Fentanyl and Alfentanil." Anesthesiology 98 (2003): 853-861
  • Yun CH, Wood M, Wood AJ, Guengerich FP "Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4: an explanation of the variable elimination clearance." Anesthesiology 77 (1992): 467-74
  • "Product Information. Alfenta (alfentanil)." Janssen Pharmaceutica, Titusville, NJ.
  • Klees TM, Sheffels P, Thummel KE, Kharasch ED "Pharmacogenetic Determinants of Human Liver Microsomal Alfentanil Metabolism and the Role of Cytochrome P450 3A5." Anesthesiology 102 (2005): 550-556
  • Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT "The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil." Anesth Analg 87 (1998): 190-4
  • Klees TM, Sheffels P, Dale O, Kharasch ED "Metabolism of alfentanil by cytochrome P4503A enzymes." Drug Metab Dispos 33 (2005): 303-11
  • Labroo RB, Thummel KE, Kunze KL, Podoll T, Trager WF, Kharasch ED "Catalytic role of cytochrome P4503A4 in multiple pathways of alfentanil metabolism." Drug Metab Dispos 23 (1995): 490-6
  • Kharasch ED, Russell M, Mautz D, Thummel KE, Kunze KL, Bowdle A, Cox K "The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions." Anesthesiology 87 (1997): 36-50
  • Yate PM, Thomas D, Short SM, Sebel PS, Morton J "Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU." Br J Anaesth 58 (1986): 1091-9
  • Kharasch ED, Thummel KE "Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance?" Anesth Analg 76 (1993): 1033-9
  • Bartkowski RR, Goldberg ME, Larijani GE, Boerner T "Inhibition of alfentanil metabolism by erythromycin." Clin Pharmacol Ther 46 (1989): 99-102
  • Koehntop DE, Noormohamed SE, Fletcher CV "Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation." Pharmacotherapy 14 (1994): 592-9
Alfenta

Generic Name: alfentanil

Brand name:

Synonyms: n.a.

PCE Dispertab

Generic Name: erythromycin

Brand name: EES. Granules, EES-400 Filmtab, EryPed 200, EryPed 400, Ery-Tab, Erythrocin Lactobionate, Erythrocin Stearate Filmtab, PCE Dispertab, E. E. S, EryPed, Erythrocin, Erythromycin Filmtabs, Erythromycin Lactobionate - IV

Synonyms: PCE Dispertab (Oral), PCE, PCE (Oral)

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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