Liverpool HEP Interactions

Do Not Coadminister

Ledipasvir/Sofosbuvir

Ombitasvir/Paritaprevir/r

Summary:

Ombitasvir/paritaprevir/ritonavir is a complete regimen. There are no data to support the coadministration with other DAAs.

Description:

Viekirax safety and efficacy have been established in combination with dasabuvir and/or ribavirin. Co-administration of Viekirax with other directly acting antivirals has not been studied and therefore cannot be recommended.
Viekirax Summary of Product Characteristics, AbbVie Ltd, January 2015.

Potential Interaction

Ledipasvir/Sofosbuvir

Amlodipine

Summary:

Coadministration has not studied but may increase concentrations of amlodipine or ledipasvir due to P-gp inhibition. Although a clinically significant effect of ledipasvir is considered unlikely, close monitoring of heart rate, blood pressure and for increased side effects of amlodipine is recommended.

Description:

(See Summary)

Potential Interaction

Ombitasvir/Paritaprevir/r

Amlodipine

Summary:

Coadministration with Viekirax alone has not been studied but a similar effect to that with Viekirax + dasabuvir is expected due to inhibition of CYP3A4 by ritonavir. Coadministration of amlodipine (5 mg single dose) with Viekirax + dasabuvir increased amlodipine AUC by 2.57-fold, with no change in ombitasvir AUC and a 22% decrease in paritaprevir AUC. Decrease amlodipine dose by 50%. Caution is warranted and close monitoring of patients is recommended.

Description:

Coadministration with Viekirax alone has not been studied but a similar effect is expected as observed with Viekirax + dasabuvir due to inhibition of CYP3A4 by ritonavir. Coadministration of amlodipine (5 mg single dose) with Viekirax + dasabuvir increased amlodipine Cmax by 26% and increased AUC by 2.57-fold. There was no change ombitasvir Cmax, AUC or Cmin. Paritaprevir Cmax, AUC and Cmin decreased by 23%, 22% and 12%, respectively. Decrease amlodipine dose by 50% and monitor patients for clinical effects.
Viekirax Summary of Product Characteristics, AbbVie Ltd, January 2015.

Potential Interaction

Ombitasvir/Paritaprevir/r

Gliclazide

Summary:

Coadministration has not been studied but gliclazide exposure may decrease when administered with ombitasvir/paritaprevir/ritonavir. Gliclazide is a substrate of CYP2C9 and CYP2C19. There was no interaction between ombitasvir/paritaprevir/ritonavir 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. An interaction of similar magnitude is expected with other CYP2C19 substrates. Close monitoring for lack of response is recommended. Increase the dose of gliclazide if needed.

Description:

(See Summary)

No Interaction Expected

Ledipasvir/Sofosbuvir

Metformin

Summary:

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Metformin is mainly excreted renally. It is transported by OCT2 which ledipasvir/sofosbuvir do not inhibit. [Note, metformin is contraindicated with hepatic insufficiency, acute alcohol intoxication, and alcoholism.]

Description:

Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV direct-acting antiviral treatment. Glucose levels of diabetic patients initiating direct-acting antiviral therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when direct-acting antiviral therapy is initiated .

Harvoni Summary of Product Characteristics, Gilead Sciences Ltd, January 2021.

Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment. Frequent monitoring of relevant laboratory parameters (e.g. blood glucose levels in diabetic patients) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Harvoni US Prescribing Information, Gilead Sciences Inc., March 2020.

No Interaction Expected

Ledipasvir/Sofosbuvir

Perindopril

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Perindopril is a prodrug metabolised in the liver to the active perindoprilat and multiple inactive metabolites. There is no evidence that these enzymes are affected by ledipasvir/sofosbuvir.

Description:

(See Summary)

No Interaction Expected

Ledipasvir/Sofosbuvir

Gliclazide

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gliclazide is metabolized by CYPs 2C19 and 2C9 which are not affected by ledipasvir.

Description:

Diabetics may experience improved glucose control, potentially resulting in symptomatic hypoglycaemia, after initiating HCV direct-acting antiviral treatment. Glucose levels of diabetic patients initiating direct-acting antiviral therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary. The physician in charge of the diabetic care of the patient should be informed when direct-acting antiviral therapy is initiated .

Harvoni Summary of Product Characteristics, Gilead Sciences Ltd, January 2021.

Clearance of HCV infection with direct acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment. Frequent monitoring of relevant laboratory parameters (e.g. blood glucose levels in diabetic patients) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary.

Harvoni US Prescribing Information, Gilead Sciences Inc., March 2020.

No Interaction Expected

Ombitasvir/Paritaprevir/r

Diclofenac

Summary:

Coadministration has not been studied. Diclofenac is a substrate of CYP2C9, CYP3A4, UGT1A9 and UGT2B7. With multiple pathways diclofenac exposure is not expected to increase with ombitasvir/paritaprevir/ritonavir. There was no interaction between and warfarin, a CYP2C9 substrate and ombitasvir/paritaprevir/ritonavir, so no interaction is expected due to CYP2C9 involvement.

Description:

(See Summary)

No Interaction Expected

Ombitasvir/Paritaprevir/r

Metformin

Summary:

Coadministration without dasabuvir has not been studied. 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

Perindopril

Summary:

Coadministration has not been studied but perindopril can be administered with ombitasvir/paritaprevir/ritonavir and no dose alteration is required. Perindopril is metabolised by hydrolysis, glucuronidation and cyclization.

Description:

(See Summary)

No Interaction Expected

Ledipasvir/Sofosbuvir

Diclofenac

Summary:

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is metabolised by CYP2C9 and is an inhibitor of the renal transporter MRP4. Ledipasvir/sofosbuvir do not affect this enzyme and are not substrates for this transporter.

Description:

(See Summary)

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