Liverpool HEP Interactions

Potential Interaction

Ombitasvir/Paritaprevir/r + Dasabuvir

Flecainide

Summary:

Coadministration has not been studied. Flecainide is a substrate of CYP2D6. Ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose, ritonavir does not markedly inhibit CYP2D6. However flecainide is a narrow therapeutic index drug and caution is advised.

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

Acenocoumarol

Summary:

Coadministration has not been studied. Acenocoumarol is a substrate of CYP2C9 and CYP1A2. Ombitasvir/paritaprevir/ritonavir at steady-state did not affect the plasma exposures of the anticoagulant warfarin which is metabolised in a similar way. However, a case report describes a patient who required a significant increase in acenocoumarol weekly dose probably due to an interaction with ombitasvir/paritaprevir/ritonavir and/or dasabuvir. Ombitasvir/paritaprevir/ritonavir and acenocoumarol can be coadministered but with close monitoring of international normalized ratio (INR) as dose modifications may be necessary in some patients.

Description:

A case was reported of a patient who required a significant increase in acenocoumarol weekly dose probably due to an interaction with ombitasvir/paritaprevir/ritonavir and/or dasabuvir. A causality assessment of the drug-drug interaction leading to a reduced INR was conducted according to the Naranjo algorithm. A score of 6 suggested that the adverse drug reaction was probable. Because of possible INR abnormalities during the concomitant use of acenocoumarol, ombitasvir/paritaprevir/ritonavir and dasabuvir, clinicians should closely monitor INR values.
Decreased INR after acenocoumarol, ombitasvir/paritaprevir/ritonavir and dasabuvir co-administration. de Lorenzo-Pinto A, Giménez-Manzorro Á, Rodríguez-González CG, et al. J Clin Pharm Ther. 2016 Aug;41(4):444-446.

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Hydrochlorothiazide

Summary:

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

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Insulin

Summary:

Coadministration has not been studied but insulin can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Insulin is metabolised by hydrolysis.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Metformin

Summary:

Coadministration with ombitasvir/paritaprevir/ritonavir +dasabuvir decreased metformin Cmax and AUC by 23% and 10%, respectively. No dosage adjustment of metformin is required. [Note, metformin is contraindicated with hepatic insufficiency, acute alcohol intoxication, and alcoholism.]

Description:

Coadministration of ombitasvir/paritaprevir/ritonavir (25/150/100 mg, once daily) + dasabuvir (250 mg, twice daily) with metformin (500 mg, single dose) was studied in 12 healthy volunteers an open-label, two-arm study. Ombitasvir Cmax decreased by 8% and AUC and Ctrough both increased by 1%. Paritaprevir Cmax and AUC decreased by 37% and 20%, respectively, while Ctrough increased by 22%. Dasabuvir Cmax, AUC, and Ctrough decreased by 17%, 14%, and 5%, respectively. Ritonavir Cmax and Ctrough decreased by 11% and 8%, respectively, while Ctrough increased by 18%. Metformin Cmax and AUC decreased by 23% and 10%, respectively. No dosage adjustment to metformin is required. The reason for the decrease in paritaprevir Cmax is unknown but is not expected to affect efficacy and no dose adjustment is required.

Drug-Drug Interactions Between the Anti-Hepatitis C Virus 3D Regimen of Ombitasvir, Paritaprevir/Ritonavir, and Dasabuvir and Eight Commonly Used Medications in Healthy Volunteers. Polepally AR, King JR, B Ding B, et al. Clin Pharmacokinet, 2016, 55(8):1003-14.

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Metoprolol

Summary:

Coadministration has not been studied but metoprolol can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Metoprolol is metabolised by CYP2D6. Ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose ritonavir does not markedly inhibit CYP2D6. [Note, in patients with severe hepatic dysfunction a reduction in dosage may be necessary.]

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Sitagliptin

Summary:

Sitagliptan can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir to subjects with normal renal function and no dose alteration is required since metabolism (including via CYP3A4), plays only a minor role in sitagliptin clearance. In severe renal impairment or end-stage renal disease (ESRD) metabolism is more important and it is possible that ritonavir could alter the pharmacokinetics of sitagliptin in such patients.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r + Dasabuvir

Captopril

Summary:

Coadministration has not been studied but captopril can be administered with ombitasvir/paritaprevir/ritonavir + dasabuvir and no dose alteration is required. Captopril is metabolised by sulfation and approximately 40-50% is excreted in the urine.

Description:

(See Summary)

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