Skip to main content

Drug Interactions between clonidine / ketorolac / ropivacaine and erythromycin

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

Edit list (add/remove drugs)

Interactions between your drugs

Minor

erythromycin ROPivacaine

Applies to: erythromycin and clonidine / ketorolac / ropivacaine

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

Drug and food interactions

Moderate

erythromycin food

Applies to: erythromycin

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

References (7)
  1. Welling PG, Huang H, Hewitt PF, Lyons LL (1978) "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci, 67, p. 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. (1979) "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci, 68, p. 150-5
  3. Welling PG (1977) "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm, 5, p. 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC (1978) "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol, 18, p. 194-202
  5. Malmborg AS (1979) "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother, 5, p. 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW (1989) "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol, 29, p. 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K (2001) "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol, 56, p. 799-803
Moderate

cloNIDine food

Applies to: clonidine / ketorolac / ropivacaine

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References (10)
  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
  9. (2023) "Product Information. Buprenorphine (buprenorphine)." G.L. Pharma UK Ltd
  10. (2023) "Product Information. Temgesic (buprenorphine)." Reckitt Benckiser Pty Ltd
Moderate

ketorolac food

Applies to: clonidine / ketorolac / ropivacaine

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References (1)
  1. (2002) "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn
Minor

erythromycin food

Applies to: erythromycin

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

References (1)
  1. Morasso MI, Chavez J, Gai MN, Arancibia A (1990) "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol, 28, p. 426-9

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.

See also

Report options

Loading...
QR code containing a link to this page

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Medical Disclaimer