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Drug Interactions between alfentanil and cyclosporine

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

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Interactions between your drugs

Moderate

cycloSPORINE ALfentanil

Applies to: cyclosporine and alfentanil

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 (17)
  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

Drug and food interactions

Moderate

cycloSPORINE food

Applies to: cyclosporine

GENERALLY AVOID: Administration with grapefruit juice (compared to water or orange juice) has been shown to increase blood concentrations of cyclosporine with a relatively high degree of interpatient variability. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

GENERALLY AVOID: Administration with red wine or purple grape juice may decrease blood concentrations of cyclosporine. In 12 healthy volunteers, 12 ounces total of a merlot consumed 15 minutes prior to and during cyclosporine administration (single 8 mg/kg dose of Sandimmune) decreased cyclosporine peak blood concentration (Cmax) and systemic exposure (AUC) by 38% and 30%, respectively, compared to water. The time to reach peak concentration (Tmax) doubled, and oral clearance increased 50%. Similarly, one study were 12 healthy patients were administered purple grape juice and a single dose of cyclosporine showed a 30% and a 36% decrease in cyclosporine systemic exposure (AUC) and peak blood concentration (Cmax), respectively. The exact mechanism of interaction is unknown but may involve decreased cyclosporine absorption.

MONITOR: Food has been found to have variable effects on the absorption of cyclosporine. There have been reports of impaired, unchanged, and enhanced absorption during administration with meals relative to the fasting state. The mechanisms are unclear. Some investigators found an association with the fat content of food. In one study, increased fat intake resulted in significantly increased cyclosporine bioavailability and clearance. However, the AUC and pharmacodynamics of cyclosporine were not significantly affected, thus clinical relevance of these findings may be minimal.

MANAGEMENT: Patients receiving cyclosporine therapy should be advised to either refrain from or avoid fluctuations in the consumption of grapefruits and grapefruit juice. Until more data are available, the consumption of red wine or purple grape juice should preferably be avoided or limited. All oral formulations of cyclosporine should be administered on a consistent schedule with regard to time of day and relation to meals so as to avoid large fluctuations in plasma drug levels.

References (13)
  1. Honcharik N, Yatscoff RW, Jeffery JR, Rush DN (1991) "The effect of meal composition on cyclosporine absorption." Transplantation, 52, p. 1087-9
  2. Ducharme MP, Provenzano R, Dehoornesmith M, Edwards DJ (1993) "Trough concentrations of cyclosporine in blood following administration with grapefruit juice." Br J Clin Pharmacol, 36, p. 457-9
  3. Bailey DG, Arnold JMO, Spence JD (1994) "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet, 26, p. 91-8
  4. Hollander AAMJ, Vanrooij J, Lentjes EGWM, Arbouw F, Vanbree JB, Schoemaker RC, Vanes LA, Vanderwoude FJ, Cohen AF (1995) "The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients." Clin Pharmacol Ther, 57, p. 318-24
  5. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  6. Tan KKC, Trull AK, Uttridge JA, Metcalfe S, Heyes CS, Facey S, Evans DB (1995) "Effect of dietary fat on the pharmacokinetics and pharmacodynamics of cyclosporine in kidney transplant recipients." Clin Pharmacol Ther, 57, p. 425-33
  7. Yee GC, Stanley DL, Pessa LJ, et al. (1995) "Effect of grrapefruit juice on blood cyclosporin concentration." Lancet, 345, p. 955-6
  8. Ducharme MP, Warbasse LH, Edwards DJ (1995) "Disposition of intravenous and oral cyclosporine after administration with grapefruit juice." Clin Pharmacol Ther, 57, p. 485-91
  9. Ioannidesdemos LL, Christophidis N, Ryan P, Angelis P, Liolios L, Mclean AJ (1997) "Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases." J Rheumatol, 24, p. 49-54
  10. Min DI, Ku YM, Perry PJ, Ukah FO, Ashton K, Martin MF, Hunsicker LG (1996) "Effect of grapefruit juice on cyclosporine pharmacokinetics in renal transplant patients." Transplantation, 62, p. 123-5
  11. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  12. Tsunoda SM, Harris RZ, Christians U, et al. (2001) "Red wine decreases cyclosporine bioavailability." Clin Pharmacol Ther, 70, p. 462-7
  13. Oliveira-Freitas VL, Dalla Costa T, Manfro RC, Cruz LB, Schwartsmann G (2010) "Influence of purple grape juice in cyclosporine availability." J Ren Nutr, 20, p. 309-13
Moderate

ALfentanil food

Applies to: 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 (9)
  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

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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