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Drug Interactions between atazanavir / cobicistat and sufentanil

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

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Interactions between your drugs

Moderate

SUFentanil atazanavir

Applies to: sufentanil and atazanavir / cobicistat

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of sufentanil, which is primarily metabolized by the isoenzyme. Increased sufentanil concentrations may enhance or prolong pharmacologic effects and potentiate the risk of central nervous system and respiratory depression. In six healthy volunteers, pretreatment with erythromycin (500 mg twice a day for 7 days) had no significant effects on the pharmacokinetics of sufentanil (3 mcg/kg single IV dose) relative to placebo in the nine hours following administration. However, in vitro data suggest that other potent CYP450 3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir) may interfere with the metabolism of sufentanil.

MANAGEMENT: Patients receiving sufentanil with potent CYP450 3A4 inhibitors should be carefully monitored for excessive central nervous system and respiratory depression, and dosage adjustments made accordingly if necessary.

References (3)
  1. Bartkowski RR, Goldberg ME, Huffnagle S, Epstein RH (1993) "Sufentanil disposition. Is it affected by erythromycin administration?" Anesthesiology, 78, p. 260-5
  2. (2001) "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals
  3. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M (1996) "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg, 82, p. 167-72
Moderate

SUFentanil cobicistat

Applies to: sufentanil and atazanavir / cobicistat

MONITOR: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of sufentanil, which is primarily metabolized by the isoenzyme. Increased sufentanil concentrations may enhance or prolong pharmacologic effects and potentiate the risk of central nervous system and respiratory depression. In six healthy volunteers, pretreatment with erythromycin (500 mg twice a day for 7 days) had no significant effects on the pharmacokinetics of sufentanil (3 mcg/kg single IV dose) relative to placebo in the nine hours following administration. However, in vitro data suggest that other potent CYP450 3A4 inhibitors (e.g., itraconazole, ketoconazole, ritonavir) may interfere with the metabolism of sufentanil.

MANAGEMENT: Patients receiving sufentanil with potent CYP450 3A4 inhibitors should be carefully monitored for excessive central nervous system and respiratory depression, and dosage adjustments made accordingly if necessary.

References (3)
  1. Bartkowski RR, Goldberg ME, Huffnagle S, Epstein RH (1993) "Sufentanil disposition. Is it affected by erythromycin administration?" Anesthesiology, 78, p. 260-5
  2. (2001) "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals
  3. Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M (1996) "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg, 82, p. 167-72

Drug and food interactions

Moderate

atazanavir food

Applies to: atazanavir / cobicistat

ADJUST DOSING INTERVAL: Administration of atazanavir with food enhances oral bioavailability and reduces pharmacokinetic variability. According to the manufacturer, administration with a light meal increased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single 400 mg dose of atazanavir by 57% and 70%, respectively, relative to the fasting state. Administration with a high-fat meal resulted in a mean increase of 35% in atazanavir AUC and no change in Cmax compared to fasting. The coefficient of variation of AUC and Cmax decreased by approximately one-half when given with either a light or high-fat meal compared to the fasting state.

MANAGEMENT: To ensure maximal oral absorption, atazanavir should be administered with or immediately after a meal.

References (1)
  1. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
Moderate

SUFentanil food

Applies to: sufentanil

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.

Further information

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