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Drug Interactions between Alfenta and avacopan

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

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Interactions between your drugs

Moderate

ALfentanil avacopan

Applies to: Alfenta (alfentanil) and avacopan

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of alfentanil, which is primarily metabolized by the isoenzyme. Alfentanil clearance has been reported to reduce significantly in the presence of moderate or potent inhibitors of CYP450 3A4 such as cimetidine, diltiazem, fluconazole, and troleandomycin. Isolated reports of prolonged sedation and respiratory depression have also been associated with concomitant use of inhibitors such as erythromycin.

MANAGEMENT: Patients receiving alfentanil in combination with CYP450 3A4 inhibitors 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

  1. Bartkowski RR, Goldberg ME, Larijani GE, Boerner T (1989) "Inhibition of alfentanil metabolism by erythromycin." Clin Pharmacol Ther, 46, p. 99-102
  2. Bartkowski RR, McDonnell TE (1990) "Prolonged alfentanil effect following erythromycin administration." Anesthesiology, 73, p. 566-8
  3. Yun CH, Wood M, Wood AJ, Guengerich FP (1992) "Identification of the pharmacogenetic determinants of alfentanil metabolism: cytochrome P-450 3A4: an explanation of the variable elimination clearance." Anesthesiology, 77, p. 467-74
  4. Yate PM, Thomas D, Short SM, Sebel PS, Morton J (1986) "Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients on the ITU." Br J Anaesth, 58, p. 1091-9
  5. (2001) "Product Information. Alfenta (alfentanil)." Janssen Pharmaceuticals
  6. Kharasch ED, Thummel KE (1993) "Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance?" Anesth Analg, 76, p. 1033-9
  7. Koehntop DE, Noormohamed SE, Fletcher CV (1994) "Effects of long-term drugs on alfentanil clearance in patients undergoing renal transplantation." Pharmacotherapy, 14, p. 592-9
  8. Labroo RB, Thummel KE, Kunze KL, Podoll T, Trager WF, Kharasch ED (1995) "Catalytic role of cytochrome P4503A4 in multiple pathways of alfentanil metabolism." Drug Metab Dispos, 23, p. 490-6
  9. Kharasch ED, Russell M, Mautz D, Thummel KE, Kunze KL, Bowdle A, Cox K (1997) "The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions." Anesthesiology, 87, p. 36-50
  10. Palkama VJ, Isohanni MH, Neuvonen PJ, Olkkola KT (1998) "The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmacodynamics of intravenous alfentanil." Anesth Analg, 87, p. 190-4
  11. Ibrahim AE, Feldman J, Karim A, Kharasch ED (2003) "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, p. 853-861
  12. Kharasch ED, Walker A, Hoffer C, Sheffels P (2004) "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, p. 452-66
  13. Klees TM, Sheffels P, Thummel KE, Kharasch ED (2005) "Pharmacogenetic Determinants of Human Liver Microsomal Alfentanil Metabolism and the Role of Cytochrome P450 3A5." Anesthesiology, 102, p. 550-556
  14. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  15. EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
  16. Klees TM, Sheffels P, Dale O, Kharasch ED (2005) "Metabolism of alfentanil by cytochrome P4503A enzymes." Drug Metab Dispos, 33, p. 303-11
  17. (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc
View all 17 references

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Drug and food interactions

Moderate

avacopan food

Applies to: avacopan

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of avacopan. When a 30 mg capsule of avacopan was administered with a high-fat, high-calorie meal, avacopan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by approximately 8% and 72%, respectively, while the time to reach peak concentration (Tmax) was delayed by approximately 4 hours (from 2.0 hours to 6.0 hours).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avacopan. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for itraconazole, a potent CYP450 3A4 inhibitor. When avacopan was administered with itraconazole (200 mg once daily for 4 days), avacopan peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 1.9-fold and 2.2-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict. Increased exposure to avacopan may increase the risk and/or severity of serious adverse reactions such as hepatotoxicity and infections.

MANAGEMENT: To ensure maximal oral absorption, avacopan should be administered with food. Patients should preferably avoid or limit consumption of grapefruit, grapefruit juice, or any supplement containing grapefruit extract during avacopan therapy.

References

  1. (2021) "Product Information. Tavneos (avacopan)." ChemoCentryx, Inc.
  2. (2023) "Product Information. Tavneos (avacopan)." Vifor Fresenius Medical Care Renal Pharma UK Ltd

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Moderate

ALfentanil food

Applies to: Alfenta (alfentanil)

GENERALLY AVOID: Ethanol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics. 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.

MANAGEMENT: Concomitant use of opioid analgesics with ethanol should be avoided.

References

  1. Linnoila M, Hakkinen S (1974) "Effects of diazepam and codeine, alone and in combination with alcohol, on simulated driving." Clin Pharmacol Ther, 15, p. 368-73
  2. Sturner WQ, Garriott JC (1973) "Deaths involving propoxyphene: a study of 41 cases over a two-year period." JAMA, 223, p. 1125-30
  3. Girre C, Hirschhorn M, Bertaux L, et al. (1991) "Enhancement of propoxyphene bioavailability by ethanol: relation to psychomotor and cognitive function in healthy volunteers." Eur J Clin Pharmacol, 41, p. 147-52
  4. Levine B, Saady J, Fierro M, Valentour J (1984) "A hydromorphone and ethanol fatality." J Forensic Sci, 29, p. 655-9
  5. Sellers EM, Hamilton CA, Kaplan HL, Degani NC, Foltz RL (1985) "Pharmacokinetic interaction of propoxyphene with ethanol." Br J Clin Pharmacol, 19, p. 398-401
  6. Carson DJ (1977) "Fatal dextropropoxyphene poisoning in Northern Ireland. Review of 30 cases." Lancet, 1, p. 894-7
  7. Rosser WW (1980) "The interaction of propoxyphene with other drugs." Can Med Assoc J, 122, p. 149-50
  8. Edwards C, Gard PR, Handley SL, Hunter M, Whittington RM (1982) "Distalgesic and ethanol-impaired function." Lancet, 2, p. 384
  9. Kiplinger GF, Sokol G, Rodda BE (1974) "Effect of combined alcohol and propoxyphene on human performance." Arch Int Pharmacodyn Ther, 212, p. 175-80
View all 9 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.

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