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Drug Interactions between dasabuvir / ombitasvir / paritaprevir / ritonavir and Naropin Novaplus

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

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Interactions between your drugs

Minor

ritonavir ROPivacaine

Applies to: dasabuvir / ombitasvir / paritaprevir / ritonavir and Naropin Novaplus (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

  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

ritonavir food

Applies to: dasabuvir / ombitasvir / paritaprevir / ritonavir

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):

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Moderate

paritaprevir food

Applies to: dasabuvir / ombitasvir / paritaprevir / ritonavir

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References

  1. "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC (2022):

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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.

See also

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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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