Liverpool HEP Interactions

Do Not Coadminister

Ombitasvir/Paritaprevir/r + Dasabuvir

Lercanidipine

Summary:

Avoid concomitant use with ombitasvir/paritaprevir/ritonavir + dasabuvir. Lercanidipine is a substrate of CYP3A4 and its exposure may increase with ritonavir, a CYP3A4 inhibitor. Ketoconazole, a strong CYP3A4 inhibitor, increased plasma levels of the eutomer S-lercanidipine (AUC by 15-fold, Cmax by 8-fold). Consequently, the lercanidipine product label says that coprescription of lercanidipine with inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir, erythromycin, troleandomycin) should be avoided.

Description:

(See Summary)

Do Not Coadminister

Ombitasvir/Paritaprevir/r + Dasabuvir

Lovastatin

Summary:

Coadministration is contraindicated. Lovastatin is a substrate of CYP3A4 and OATP1B1. Exposure of lovastatin may increase due to CYP3A4 inhibition by ritonavir causing potential for serious reactions such as risk of myopathy including rhabdomyolysis.

Description:

Concomitant use is contraindicated. Coadministration has not been studied but is expected to increase concentrations of lovastatin due to inhibition of CYP3A4 and OATP1B. Medicinal products that are highly dependent on CYP3A for clearance and for which elevated plasma levels are associated with serious events, such as lovastatin, must not be co-administered.
Viekirax Summary of Product Characteristics, AbbVie Ltd, January 2015.

Coadministration is contraindicated due to the potential for myopathy including rhabdomyolysis.

Viekira Pak US Prescribing Information, AbbVie, December 2014.

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Nirmatrelvir/ritonavir (Paxlovid)

Summary:

Coadministration has not been studied. Patients on ritonavir-containing HCV regimens should continue their treatment with no dosage modification. Monitor for increased nirmatrelvir/ritonavir or HCV drug adverse events with concomitant use. Coadministration may increase ombitasvir, paritaprevir and dasabuvir concentrations.

Description:

Concomitant therapy with ritonavir-containing regimen - no dose adjustment is needed; the dose of Paxlovid is 300 mg/100 mg twice daily for 5 days. Patients diagnosed with hepatitis C virus (HCV) infection who are receiving ritonavir-containing regimen should continue their treatment as indicated.

Paxlovid Summary of Product Characteristics, Pfizer Ltd, February 2022.

No dosage adjustment is required when co-administered with other products containing ritonavir or cobicistat. Patients on ritonavir- containing HCV regimens should continue their treatment as indicated. Monitor for increased Paxlovid or HCV drug adverse events with concomitant use. Coadministration may increase ombitasvir and paritaprevir concentrations. Refer to the ombitasvir/paritaprevir/ritonavir label for further information.

Paxlovid FDA Emergency Use Authorisation, Pfizer Inc, April 2022.

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Letrozole

Summary:

Coadministration has not been studied but letrozole is a substrate of CYP3A4. Exposure of letrozole may increase due to inhibition CYP3A4 by ritonavir. Caution is advised and a dose titration may be required.

Description:

(See Summary)

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Lidocaine (Lignocaine)

Summary:

Coadministration has not been studied. Lidocaine is a substrate of CYP3A4. Exposure of lidocaine may increase due to CYP3A4 inhibition by ritonavir causing adverse effects (common adverse reactions are those from the central and peripheral nervous system). Therapeutic concentration monitoring should be done for lidocaine and a decrease in lidocaine dose maybe needed. Topical lidocaine can be used since there is minimal systemic absorption and adverse effects are averted.

Description:

Coadministration may increase concentrations of this antiarrhythmic. Caution is warranted and therapeutic concentration monitoring (if available) is recommended for antiarrhythmics when co-administered.

Viekira Pak US Prescribing Information, AbbVie, December 2014.

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Ecstasy (MDMA)

Summary:

Coadministration has not been studied. MDMA (Ecstasy) is metabolised by CYP2D6; ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose it does not appear to markedly inhibit CYP2D6. However there have been fatalities reported in subjects taking ritonavir-boosted HIV protease inhibitors and MDMA. Caution is strongly advised.

Description:

(See Summary)

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Gliclazide

Summary:

Coadministration has not been studied but gliclazide exposure may decrease when administered with ombitasvir/paritaprevir/ritonavir + dasabuvir. Gliclazide is a substrate of CYP2C9 and CYP2C19. There was no interaction between ombitasvir/paritaprevir/ritonavir + dasabuvir and warfarin (a CYP2C9 substrate) so no interaction is expected due to CYP2C9 involvement. However, exposure of omeprazole (a model CYP2C19 substrate) decreased by 40-50% with ombitasvir/paritaprevir/ritonavir + dasabuvir. An interaction of similar magnitude is expected with other CYP2C19 substrates. Close monitoring is recommended for lack of response. Increase the dose of gliclazide if needed.

Description:

(See Summary)

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Dexamfetamine

Summary:

Coadministration has not been studied. The role of CYP450 in the metabolism of dexamfetamine has not been fully described and potent inhibitors of CYP3A4, such as ritonavir, should be used with caution.

Description:

(See Summary)

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Molly (Ecstasy, MDMA)

Summary:

Coadministration has not been studied. MDMA (Ecstasy) is metabolised by CYP2D6; ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose it does not appear to markedly inhibit CYP2D6. However there have been fatalities reported in subjects taking ritonavir-boosted HIV protease inhibitors and MDMA. Caution is strongly advised.

Description:

(See Summary)

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Aripiprazole

Summary:

Coadministration has not been studied. Aripiprazole is a substrate of CYP3A4 and CYP2D6. Aripiprazole exposure may increase due to CYP3A4 inhibition by ritonavir. Close monitoring is recommended. A decrease in aripiprazole dose may be needed. The aripiprazole label suggests decreasing the dose by one-half when administered with CYP3A4 inhibitors like ketoconazole.

Description:

(See Summary)

Potential Weak Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Bupropion

Summary:

Coadministration has not been studied. No interaction was observed between ombitasvir/paritaprevir/ritonavir + dasabuvir and methadone (CYP2B6 substrate). Hence, it is not expected to interact with other CYP2B6 substrates. Short-term ritonavir (200 mg; 4 doses over 2 days) dosing has only minimal impact on the pharmacokinetics of bupropion while long term administration of low dose ritonavir (100 mg twice daily) doses has shown only ≤22% decrease in bupropion exposures. Monitoring may be required. Adjust bupropion dose if clinically indicated.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Chlortalidone

Summary:

Coadministration has not been studied but chlortalidone can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Chlortalidone is mainly excreted in urine.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Desloratadine

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolism of desloratidine is poorly characterised and no clinically relevant interaction have been observed with other inhibitors of CYP enzymes.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Ceftriaxone

Summary:

Coadministration has not been studied but ceftriaxone can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Ceftriaxone is mainly excreted in urine.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Bilastine

Summary:

Coadministration has not been studied but bilastine can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Bilastine is not significantly metabolized and is mainly excreted in the urine. In-vitro studies show that bilastine is a substrate of P-gp, but as there is no significant interaction between ombitasvir/paritaprevir/ritonavir + dasabuvir and digoxin (a model P-gp substrate), no potential interaction due to P-gp involvement is expected with bilastine.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Kava kava (Piper methysticum)

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Kava kava appears to inhibit CYP3A4 in vitro only, therefore, a clinically relevant effect is not expected. However, monitor patient as variations in potency amongst preparations is large.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Azilsartan

Summary:

Azilsartan can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Azilsartan is a substrate of CYP2C9 but there was no interaction between ombitasvir/paritaprevir/ritonavir + dasabuvir and warfarin, a CYP2C9 substrate. Therefore, no interaction is expected with azilsartan.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Lymecycline

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically relevant drug interaction is unlikely. Lymecycline is not metabolised and is excreted unchanged by renal and biliary routes.

Description:

(See Summary)

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