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Drug Interactions between indinavir and ropivacaine / sufentanil

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

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Interactions between your drugs

Moderate

SUFentanil indinavir

Applies to: ropivacaine / sufentanil and indinavir

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

  1. Bartkowski RR, Goldberg ME, Huffnagle S, Epstein RH "Sufentanil disposition. Is it affected by erythromycin administration?" Anesthesiology 78 (1993): 260-5
  2. "Product Information. Sufenta (sufentanil)." Janssen Pharmaceuticals PROD (2001):
  3. 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

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Minor

indinavir ROPivacaine

Applies to: indinavir and ropivacaine / sufentanil

Coadministration with inhibitors of CYP450 3A4 may modestly increase the plasma concentrations of ropivacaine. Although ropivacaine is primarily metabolized by CYP450 1A2, it has been shown to undergo some metabolism via CYP450 3A4. In eight healthy volunteers, pretreatment with the 3A4 inhibitor erythromycin (500 mg three times a day for 6 days) was found to have only minor effects on the pharmacokinetics of a single dose of ropivacaine (0.6 mg/kg IV over 30 minutes) compared to placebo. However, in combination with the potent 1A2 inhibitor fluvoxamine (100 mg daily), erythromycin further increased the area under the plasma concentration-time curve (AUC) of ropivacaine by 50% compared to fluvoxamine alone, which increased the ropivacaine AUC by 3.7-fold. Fluvoxamine alone prolonged the elimination half-life of ropivacaine from 2.3 to 7.4 hours, while the addition of erythromycin further increased the half-life to 11.9 hours. In another study, pretreatment with the potent 3A4 inhibitor ketoconazole (100 mg twice daily for 2 days) decreased the mean total plasma clearance of ropivacaine (40 mg IV over 20 minutes) by just 15% in 12 healthy volunteers. Thus, it appears that CYP450 3A4 inhibitors may only have a significant effect on the pharmacokinetics of ropivacaine in the presence of a CYP450 1A2 inhibitor such as fluvoxamine, ciprofloxacin, or mexiletine.

References

  1. Halldin MM, Bredberg E, Angelin B, Arvidsson T, Askemark Y, Elofsson S, Widman M "Metabolism and excretion of ropivacaine in humans." Drug Metab Dispos 24 (1996): 962-8
  2. Oda Y, Furuichi K, Tanaka K, Hiroi T, Imaoka S, Asada A, Fujimori M, Funae Y "Metabolism of a new local anesthetic, ropivacaine, by human hepatic cytochrome P450." Anesthesiology 82 (1995): 214-20
  3. "Product Information. Naropin (ropivacaine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  4. McClure JH "Ropivacaine." Br J Anaesth 76 (1996): 300-7
  5. Ekstrom G, Gunnarsson UB "Ropivacaine, a new amide-type local anesthetic agent, is metabolized by cytochromes P450 1A and 3A in human liver microsomes." Drug Metab Dispos 24 (1996): 955-61
  6. Arlander E, Ekstrom G, Alm C, Carrillo JA, Bielenstein M, Bottiger Y, Bertilsson L, Gustafsson LL "Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3A4: An interaction study with fluvoxamine and ketoconazole as in vivo inhibitors." Clin Pharmacol Ther 64 (1998): 484-91
  7. Jokinen MJ, Ahonen J, Neuvonen PJ, Olkkola KT "The effect of erythromycin, fluvoxamine, and their combination on the pharmacokinetics of ropivacaine." Anesth Analg 91 (2000): 1207-12
View all 7 references

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Drug and food interactions

Moderate

indinavir food

Applies to: indinavir

ADJUST DOSING INTERVAL: According to the manufacturer, coadministration with a meal high in calories, fat, and protein reduces the absorption of indinavir. In ten patients given indinavir in this manner, the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of indinavir decreased by an average of 84% and 77%, respectively. In contrast, grapefruit juice may have only minor effects on the oral bioavailability of indinavir. The manufacturer's package labeling states that administration of a single 400 mg dose of indinavir with 8 oz. of grapefruit juice decreased indinavir AUC by an average of 26%. Likewise, a study consisting of 14 HIV-infected subjects found no uniform nor significant changes in steady-state indinavir AUC during administration with double-strength grapefruit juice compared to water. There was, however, a delay in absorption (Tmax) due to grapefruit juice that is unlikely to be of clinical significance.

MANAGEMENT: To ensure maximal oral absorption, indinavir should be administered without food but with water 1 hour before or 2 hours after a meal. Alternatively, indinavir may be administered with other liquids such as skim milk, juice, coffee, or tea, or with a light meal (e.g., dry toast with jelly, juice, and coffee with skim milk and sugar; corn flakes, skim milk and sugar).

References

  1. "Product Information. Crixivan (indinavir)." Merck & Co., Inc PROD (2001):
  2. Yeh KC, Deutsch PJ, Haddix H, Hesney M, Hoagland V, Ju WD, Justice SJ, Osborne B, Sterrett AT, Stone JA, Woolf E, Waldman S "Single-dose pharmacokinetics of indinavir and the effect of food." Antimicrob Agents Chemother 42 (1998): 332-8
  3. Shelton MJ, Wynn HE, Newitt RG, DiFrancesco R "Effects of grapefruit juice on pharmacokinetic exposure to indinavir in HIV-positive subjects." J Clin Pharmacol 41 (2001): 435-42

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Moderate

SUFentanil food

Applies to: ropivacaine / 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

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

Further information

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