OLYSIO™（simeprevir）获美国FDA批准及欧盟批准用于治疗慢性丙型肝炎的治疗组合
OLYSIO™（simeprevir），是一个NS3/4A蛋白酶抑制剂，慢性丙型肝炎感染的治疗，抗病毒治疗方案与聚乙二醇干扰素和利巴韦林基因型1感染的成人与代偿性肝病，包括肝硬化合并的一部分。OLYSIO TM可造福患者的慢性丙型肝炎，包括那些谁是初次接受治疗或谁没有事先干扰素为基础的治疗。
OLYSIO 150mg hard capsules
1. Name of the medicinal product
OLYSIO 150 mg hard capsules
Each hard capsule contains simeprevir sodium equivalent to 150 mg of simeprevir.
Excipient with known effect: each capsule contains 78.4 mg of lactose (as monohydrate).
For the full list of excipients, see section 6.1.
Hard capsule (capsule)
White gelatin capsule of approximately 22 mm in length, marked with “TMC435 150” in black ink.
OLYSIO is indicated in combination with other medicinal products for the treatment of chronic hepatitis C (CHC) in adult patients (see sections 4.2, 4.4 and 5.1).
For hepatitis C virus (HCV) genotype specific activity, see sections 4.4 and 5.1.
Treatment with OLYSIO should be initiated and monitored by a physician experienced in the management of CHC.
Posology
The recommended dosage of OLYSIO is one capsule of 150 mg once daily for 12 weeks, taken with food.
OLYSIO must not be administered as monotherapy. OLYSIO must be used in combination with other medicinal products for the treatment of CHC (see section 5.1). When considering OLYSIO combination treatment with peginterferon alfa and ribavirin in HCV genotype 1a patients, patients should be tested for the presence of virus with the NS3 Q80K polymorphism before starting treatment (see section 4.4).
Refer also to the Summary of Product Characteristics of the medicinal products that are used in combination with OLYSIO.
The recommended co-administered medicinal product(s) and treatment duration for OLYSIO combination therapy are provided in table 1.
Table 1: Recommended co-administered medicinal product(s) and treatment duration for OLYSIO combination therapy
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Patient population
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Treatment
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Duration
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Treatment-naïve and prior relapse patients with HCV genotype 1 or 41
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OLYSIO + peginterferon alfa + ribavirin2
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24 weeks3
Treatment with OLYSIO must be initiated in combination with peginterferon alfa and ribavirin and administered for 12 weeks and then followed by an additional 12 weeks of peginterferon alfa and ribavirin.
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Prior non-responder patients (including partial and null responders) with HCV genotype 1 or 41
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OLYSIO + peginterferon alfa + ribavirin2
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48 weeks
Treatment with OLYSIO must be initiated in combination with peginterferon alfa and ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa and ribavirin.
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Patients with HCV genotype 1 or 4, regardless of prior treatment history4
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OLYSIO + sofosbuvir
(+/- ribavirin)5
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12 weeks (see sections 4.4, 4.8 and 5.1)
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1 Includes patients with or without cirrhosis and those co-infected with human immunodeficiency virus (HIV). Relapse or non-response following prior treatment with interferon (pegylated or non-pegylated), with or without ribavirin (see section 5.1).
2 When considering OLYSIO combination treatment with peginterferon alfa and ribavirin in HCV genotype 1a patients, testing for NS3 Q80K polymorphism should be performed before starting treatment (see section 4.4).
3 Treatment-naïve and prior relapse patients with cirrhosis who are co-infected with HIV should receive 48 weeks of treatment. Treatment with OLYSIO must be initiated in combination with peginterferon alfa and ribavirin and administered for 12 weeks and then followed by an additional 36 weeks of peginterferon alfa and ribavirin. See Special patient populations - HCV/Human immunodeficiency virus type 1 (HIV-1) co-infection.
4 Includes treatment-naive patients or patients who failed prior treatment with peginterferon alfa and ribavirin with or without cirrhosis.
5 OLYSIO with sofosbuvir should only be used in patients who are intolerant to or ineligible for interferon therapy, and are in urgent need of treatment. Ribavirin could be added based on a clinical assessment of each individual patient (see sections 4.4, 4.8 and 5.1). The recommended treatment duration is 12 weeks. A longer treatment duration (up to 24 weeks) of OLYSIO with sofosbuvir (with or without ribavirin) could be considered based on an individual basis (see sections 4.4, 4.8 and 5.1).
Refer to table 2 for treatment stopping rules based on HCV RNA levels at weeks 4, 12 and 24 for patients receiving treatment with OLYSIO, peginterferon alfa and ribavirin.
Treatment discontinuation in patients with inadequate on-treatment virologic response during treatment with OLYSIO, peginterferon alfa and ribavirin
It is unlikely that patients with inadequate on-treatment virologic response will achieve a sustained virologic response (SVR), therefore discontinuation of treatment is recommended in these patients. The HCV RNA thresholds that trigger discontinuation of treatment (i.e., treatment stopping rules) are presented in table 2.
Table 2: Treatment stopping rules in patients receiving OLYSIO in combination with peginterferon alfa and ribavirin with inadequate on-treatment virologic response
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HCV RNA
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Action
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Treatment week 4: ≥ 25 IU/ml
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Discontinue OLYSIO, peginterferon alfa and ribavirin
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Treatment week 12: detectable1
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Discontinue peginterferon alfa and ribavirin (treatment with OLYSIO is complete at week 12)
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Treatment week 24: detectable1
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Discontinue peginterferon alfa and ribavirin
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1 Re-eva luation of HCV RNA is recommended in case of detectable HCV RNA after previous undetectable HCV RNA to confirm HCV RNA levels prior to discontinuing HCV treatment.
There are no virologic treatment stopping rules that apply to the combination of OLYSIO with sofosbuvir.
Dosage adjustment or interruption of OLYSIO treatment
To prevent treatment failure, the dose of OLYSIO must not be reduced or interrupted. If treatment with OLYSIO is discontinued because of adverse reactions or inadequate on-treatment virologic response, OLYSIO treatment must not be reinitiated.
Dosage adjustment or interruption of medicinal products used in combination with OLYSIO for the treatment of CHC
If adverse reactions, potentially related to the medicinal products that are used in combination with OLYSIO for the treatment of CHC, require dosage adjustment or interruption of either medicinal product, refer to the instructions outlined in the respective Summary of Product Characteristics for these medicinal products.
If the other medicinal products that are used in combination with OLYSIO for the treatment of CHC are permanently discontinued for any reason, OLYSIO must also be discontinued.
Missed dose
If a dose of OLYSIO is missed, and the patient notices within 12 hours of the usual dosing time, the patient should take the missed dose of OLYSIO with food as soon as possible and then take the next dose of OLYSIO at the regularly scheduled time.
If a dose of OLYSIO is missed by more than 12 hours after the usual dosing time, the patient should not take the missed dose of OLYSIO and should resume dosing of OLYSIO with food at the regularly scheduled time.
Special populations
Elderly (over 65 years of age)
There are limited data on the safety and efficacy of OLYSIO in patients older than 65 years. There are no safety and efficacy data of OLYSIO in patients over the age of 75 years. No dose adjustment of OLYSIO is required in elderly patients (see section 5.2).
Renal impairment
No dose adjustment of OLYSIO is required in patients with mild or moderate renal impairment. Increased simeprevir exposures have been observed in individuals with severe renal impairment. OLYSIO has not been studied in HCV infected patients with severe renal impairment (creatinine clearance below 30 ml/min) or end stage renal disease, including patients requiring haemodialysis. As exposure may be increased in HCV infected patients with severe renal impairment, caution is recommended when prescribing OLYSIO to these patients (see section 5.2).
Refer to the respective Summary of Product Characteristics of the medicinal products used in combination with OLYSIO regarding use in patients with renal impairment.
Hepatic impairme
No dose adjustment of OLYSIO is required in patients with mild or moderate hepatic impairment (Child-Pugh class A or B). Simeprevir exposure is significantly increased in subjects with severe hepatic impairment (Child-Pugh class C) and no dose recommendation can be given for those patients (see section 5.2). The safety and efficacy of OLYSIO have not been studied in HCV infected patients with moderate or severe hepatic impairment (Child-Pugh class B or C); therefore particular caution is recommended when prescribing OLYSIO to HCV infected patients with moderate or severe hepatic impairment.
Refer to the respective Summary of Product Characteristics of the medicinal products used in combination with OLYSIO regarding use in patients with decompensated cirrhosis (Child-Pugh class B or C).
Race
Given limited data, the potential risks and benefits of OLYSIO 150 mg should be carefully considered prior to use in East Asian patients (see section 5.2).
Paediatric population
The safety and efficacy of OLYSIO in children aged below 18 years have not yet been established. No data are available.
HCV/Human immunodeficiency virus type 1 (HIV-1) co-infection
No dose adjustment of OLYSIO is required in HCV/HIV-1 co-infected patients (see sections 4.8, 5.1 and 5.2).
HCV/HIV-1 co-infected patients, irrespective of prior HCV treatment history, should be treated in the same way as HCV mono-infected patients, except for co-infected patients with cirrhosis who should receive 36 weeks of treatment with peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 48 weeks).
Please refer to sections 4.4 and 4.5 for relevant interactions with antiretroviral agents.
Method of administration
OLYSIO must be taken orally once a day with food (see section 5.2). The capsule should be swallowed as a whole.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
General
The efficacy of OLYSIO has not been studied in patients with HCV genotypes 2, 3, 5 or 6; therefore OLYSIO should not be used in these patients (see section 5.1).
OLYSIO must not be administered as monotherapy and must be prescribed in combination with other medicinal products for the treatment of CHC.
If the other medicinal products that are used in combination with OLYSIO for the treatment of CHC are permanently discontinued, OLYSIO should also be discontinued (see section 4.2). Consult the Summary of Product Characteristics of the co-prescribed medicinal products before starting therapy with OLYSIO. Warnings and precautions related to these medicinal products also apply to their use in OLYSIO combination treatment.
There are no clinical data on the use of OLYSIO in re-treating patients who have failed an HCV NS3-4A protease inhibitor-based therapy (see sections 5.1 and 5.3).
Use of simeprevir in patients infected with HCV genotype 1a
Simeprevir efficacy in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with hepatitis C genotype 1a with the NS3 Q80K polymorphism at baseline compared to patients with hepatitis C genotype 1a without the Q80K polymorphism (see section 5.1). Testing for the presence of the Q80K polymorphism in patients with HCV genotype 1a is strongly recommended when considering therapy with OLYSIO in combination with peginterferon alfa and ribavirin. Alternative therapy should be considered for patients infected with HCV genotype 1a with the Q80K polymorphism or in cases where testing is not accessible.
Data are too limited to eva luate whether the presence of Q80K polymorphism in HCV genotype 1a patients reduces the efficacy of simeprevir when OLYSIO is used in combination with other direct acting antivirals against HCV (see section 5.1). Until confirmatory data becomes available, testing for the presence of the Q80K polymorphism should be considered before initiating OLYSIO in combination with sofosbuvir in patients infected with HCV genotype 1a.
Interferon-free therapy
Interferon-free regimens with OLYSIO have not been investigated in phase 3 studies (see section 5.1). The optimal regimen and treatment duration have not been established. Interferon-free therapy with OLYSIO should only be used in patients who are intolerant to or ineligible for interferon therapy, and are in urgent need of treatment.
Co-administration with other direct acting antivirals against HCV
OLYSIO should only be co-administered with other direct acting antiviral medicinal products if the benefits are considered to outweigh the risks based upon available data. There are no data to support the co-administration of OLYSIO and telaprevir or boceprevir. These HCV protease inhibitors are anticipated to be cross-resistant, and co-administration is not recommended (see also section 4.5).
OLYSIO in combination with peginterferon alfa-2b
In the clinical studies, patients randomised to simeprevir in combination with peginterferon alfa-2b and ribavirin obtained numerically lower SVR12 rates and also experienced viral breakthrough and viral relapse more frequently than those treated with simeprevir in combination with peginterferon alfa-2a and ribavirin (see section 5.1).
Pregnancy and contraception
OLYSIO should only be used during pregnancy or in women of childbearing potential if the benefit justifies the risk. Female patients of childbearing potential must use an effective form of contraception (see section 4.6).
The contraindications and warnings regarding pregnancy and contraception requirements applicable to the co-administered medicinal products also apply to their use in OLYSIO combination treatment.
Ribavirin may cause birth defects and/or death of the exposed foetus. Therefore, extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients (see section 4.6).
Photosensitivity
Photosensitivity reactions have been observed with OLYSIO combination treatment (see section 4.8). Patients should be informed of the risk of photosensitivity reactions and on the importance of applying appropriate sun protective measures during treatment with OLYSIO. Excess exposure to sun and use of tanning devices during treatment with OLYSIO should be avoided. If photosensitivity reactions occur, discontinuation of OLYSIO should be considered and patients should be monitored until the reaction has resolved.
Rash
Rash has been observed with OLYSIO combination treatment (see section 4.8). Patients with mild to moderate rashes should be monitored for possible progression of rash, including the development of mucosal signs or systemic symptoms. In case of severe rash, OLYSIO and other co-administered medicinal products for the treatment of CHC should be discontinued and the patients should be monitored until the symptoms have resolved.
Hepatic impairment
Simeprevir plasma exposure is significantly increased in subjects with severe hepatic impairment (Child-Pugh class C). The safety and efficacy of OLYSIO have not been studied in HCV infected patients with moderate or severe hepatic impairment (Child-Pugh class B or C) or in decompensated patients; therefore particular caution is recommended when prescribing OLYSIO to these patients (see sections 4.2 and 5.2).
Laboratory testing during treatment with OLYSIO, peginterferon alfa and ribavirin
HCV RNA levels should be monitored at weeks 4 and 12 and as clinically indicated (see also guidelines for treatment duration and stopping rules; section 4.2). Use of a sensitive quantitative HCV RNA assay for monitoring HCV RNA levels during treatment is recommended.
Refer to the Summary of Product Characteristics of peginterferon alfa and ribavirin for baseline, on-treatment and post-treatment laboratory testing requirements including haematology, biochemistry (including hepatic enzymes and bilirubin), and pregnancy testing requirements.
Interactions with medicinal products
Co-administration of OLYSIO with substances that moderately or strongly induce or inhibit cytochrome P450 3A (CYP3A4) is not recommended as this may lead to significantly lower or higher exposure of simeprevir, respectively.
Please refer to section 4.5 for information on interactions with medicinal products.
Hepatitis B Virus (HBV) co-infection
The safety and efficacy of OLYSIO for the treatment of HCV infection in patients co-infected with HBV have not been studied.
Organ transplant patients
The safety and efficacy of OLYSIO have not been studied in organ transplant patients.
Excipient of OLYSIO capsules
OLYSIO capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Medicinal products that affect simeprevir exposure
The primary enzyme involved in the biotransformation of simeprevir is CYP3A4 (see section 5.2) and clinically relevant effects of other medicinal products on simeprevir pharmacokinetics via CYP3A4 may occur. Co-administration of OLYSIO with moderate or strong inhibitors of CYP3A4 may significantly increase the plasma exposure of simeprevir, while co-administration with moderate or strong inducers of CYP3A4 may significantly reduce the plasma exposure of simeprevir and lead to loss of efficacy (see table 3). Therefore, co-administration of OLYSIO with substances that moderately or strongly inhibit or induce CYP3A4 is not recommended.
Hepatic uptake of simeprevir is mediated by OATP1B1. Inhibitors of OATP1B1 such as eltrombopag or gemfibrozil may result in mild increases in simeprevir plasma concentrations.
Medicinal products that are affected by the use of simeprevir
Simeprevir mildly inhibits the CYP1A2 activity and intestinal CYP3A4 activity, while it does not affect hepatic CYP3A4 activity. Co-administration of OLYSIO with medicinal products that are primarily metabolised by CYP3A4 may result in increased plasma concentrations of such medicinal products (see table 3). Simeprevir does not affect CYP2C9, CYP2C19 or CYP2D6 in vivo.
Simeprevir inhibits OATP1B1 and P-gp transporters. Co-administration of OLYSIO with medicinal products that are substrates for OATP1B1 and P-gp transport may result in increased plasma concentrations of such medicinal products (see table 3).
Interaction table
Established and theoretical interactions between simeprevir and selected medicinal products are listed in table 3 (least square mean ratios with 90% confidence intervals (90% CI) are presented, increase is indicated as “↑”, decrease as “↓”, no change as “↔”). Interaction studies have been performed in healthy adults with the recommended dose of 150 mg simeprevir once daily unless otherwise noted.
Table 3: Interactions and dose recommendation with other medicinal products
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Medicinal products by therapeutic areas
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Effect on drug levels
Least Squares Mean Ratio (90%CI)
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Recommendation for co-administration
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ANALEPTIC
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Caffeine
150 mg
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caffeine AUC 1.26 (1.21-1.32) ↑
caffeine Cmax 1.12 (1.06-1.19) ↔
caffeine Cmin not studied
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No dose adjustment is required.
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ANTIARRHYTHMICS
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Digoxin
0.25 mg
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digoxin AUC 1.39 (1.16-1.67) ↑
digoxin Cmax 1.31 (1.14-1.51) ↑
digoxin Cmin not studied
(inhibition of P-gp transporter)
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Concentrations of digoxin should be monitored and used for titration of digoxin dose to obtain the desired clinical effect.
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Amiodarone
Disopyramide
Flecainide
Mexiletine
Propafenone
Quinidine
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Not studied. Mild increases in concentrations of these antiarrhythmics may be expected when these medicinal products are administered orally.
(intestinal CYP3A4 enzyme inhibition)
Mild increases in simeprevir concentrations may occur due to inhibition of CYP3A4 by amiodarone.
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Caution is warranted and therapeutic drug monitoring for these antiarrhythmics and/or clinical monitoring (ECG etc.) when orally administered are recommended.
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ANTICOAGULANTS
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Warfarin
10 mg
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S-warfarin AUC 1.04 (1.00-1.07) ↔
S-warfarin Cmax 1.00 (0.94-1.06) ↔
S-warfarin Cmin not studied
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No dose adjustment is required. However, it is recommended that the international normalised ratio (INR) be monitored.
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ANTICONVULSANTS
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Carbamazepine
Oxcarbazepine
Phenobarbital
Phenytoin
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Not studied. Significant decrease in plasma concentrations of simeprevir are expected.
(strong CYP3A4 induction)
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It is not recommended to co-administer OLYSIO with these anticonvulsants as co-administration may result in loss of therapeutic effect of OLYSIO.
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ANTIDEPRESSANTS
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Escitalopram
10 mg once daily
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escitalopram AUC 1.00 (0.97-1.03) ↔
escitalopram Cmax 1.03 (0.99-1.07) ↔
escitalopram Cmin 1.00 (0.95-1.05) ↔
simeprevir AUC 0.75 (0.68-0.83) ↓
simeprevir Cmax 0.80 (0.71-0.89) ↓
simeprevir Cmin 0.68 (0.59-0.79) ↓
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No dose adjustment is required.
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ANTIHISTAMINES
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Astemizole
Terfenadine
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Not studied. Astemizole and terfenadine have the potential for cardiac arrhythmias. Mild increases in concentrations of these antihistamines may be expected.
(intestinal CYP3A4 enzyme inhibition)
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It is not recommended to co-administer OLYSIO with astemizole or terfenadine.
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ANTI-INFECTIVES
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Antibiotics (systemic administration)
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Azithromycin
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Not studied. Based on the elimination pathway of azithromycin, no drug interactions are expected between azithromycin and simeprevir.
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No dose adjustment is required.
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Erythromycin
500 mg three times a day
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erythromycin AUC 1.90 (1.53-2.36) ↑
erythromycin Cmax 1.59 (1.23-2.05) ↑
erythromycin Cmin 3.08 (2.54-3.73) ↑
simeprevir AUC 7.47 (6.41-8.70) ↑
simeprevir Cmax 4.53 (3.91-5.25) ↑
simeprevir Cmin 12.74 (10.19-15.93) ↑
(inhibition of CYP3A4 enzymes and P-gp transporter by both erythromycin and simeprevir)
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It is not recommended to co-administer OLYSIO with systemic erythromycin.
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Clarithromycin
Telithromycin
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Not studied. Increased plasma concentrations of simeprevir are expected.
(strong CYP3A4 enzyme inhibition)
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It is not recommended to co-administer OLYSIO with clarithromycin or telithromycin.
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Antifungals (systemic administration)
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Itraconazole
Ketoconazole*
Posaconazole
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Not studied. Significant increases in plasma concentrations of simeprevir are expected.
(strong CYP3A4 enzyme inhibition)
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It is not recommended to co-administer OLYSIO with systemic itraconazole, ketoconazole or posaconazole.
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Fluconazole
Voriconazole
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Not studied. Significant increases in plasma concentrations of simeprevir are expected.
(mild to moderate CYP3A4 enzyme inhibition)
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It is not recommended to co-administer OLYSIO with systemic fluconazole or voriconazole.
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Antimycobacterials
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Bedaquiline
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Not studied. No clinically relevant drug-drug interaction is expected.
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No dose adjustment is required.
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Rifampicin1
600 mg once daily
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rifampicin AUC 1.00 (0.93-1.08) ↔
rifampicin Cmax 0.92 (0.80-1.07) ↔
rifampicin Cmin not studied
25-desacetyl-rifampicin AUC 1.24 (1.13-1.36) ↑
25-desacetyl-rifampicin Cmax 1.08 (0.98-1.19) ↔
25-desacetyl-rifampicin Cmin not studied
simeprevir AUC 0.52 (0.41-0.67) ↓
simeprevir Cmax 1.31 (1.03-1.66) ↑
simeprevir Cmin 0.08 (0.06-0.11) ↓
(CYP3A4 enzyme induction)
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It is not recommended to co-administer OLYSIO with rifampicin as co-administration may result in loss of therapeutic effect of OLYSIO.
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Rifabutin
Rifapentine
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Not studied. Significant decreases in plasma concentrations of simeprevir are expected.
(CYP3A4 enzyme induction)
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It is not recommended to co-administer OLYSIO with rifabutin or rifapentine as co-administration may result in loss of therapeutic effect of OLYSIO.
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ANTITUSSIVE
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Dextromethorphan (DXM)
30 mg
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DXM AUC 1.08 (0.87-1.35) ↑
DXM Cmax 1.21 (0.93-1.57) ↑
DXM Cmin not studied
dextrorphan AUC 1.09 (1.03-1.15) ↔
dextrorphan Cmax 1.03 (0.93-1.15) ↔
dextrorphan Cmin not studied
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No dose adjustment is required.
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CALCIUM CHANNEL BLOCKERS (oral administration)
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Amlodipine
Bepridil
Diltiazem
Felodipine
Nicardipine
Nifedipine
Nisoldipine
Verapamil
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Not studied. Increased plasma concentrations of orally administered calcium channel blockers may be expeced.
(intestinal CYP3A4 enzyme and P-gp transporter inhibition)
Increased simeprevir concentrations may occur due to mild inhibition of CYP3A4 by amlodipine and moderate inhibition of CYP3A4 by diltiazem and verapamil.
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Caution is warranted and clinical monitoring of patients is recommended when these calcium channel blockers are given orally.
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GLUCOCORTICOIDS
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Dexamethasone (systemic)
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Not studied. Decreased plasma concentrations of simeprevir are expected.
(moderate CYP3A4 enzyme induction)
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It is not recommended to co-administer OLYSIO with systemic dexamethasone as co-administration may result in loss of therapeutic effect of OLYSIO.
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Budesonide
Fluticasone
Methylprednisolone
Prednisone
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Not studied. No clinically relevant drug-drug interaction is expected.
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No dose adjustment is required.
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GASTROINTESTINAL PRODUCTS
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Antacid
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e.g., Aluminium or Magnesium hydroxide, Calcium carbonate
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Not studied. No clinically relevant drug-drug interaction is expected.
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No dose adjustment is required.
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H2-receptor antagonists
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e.g., Cimetidine, Nizatidine, Ranitidine
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Not studied. No clinically relevant drug-drug interaction is expected.
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No dose adjustment is required.
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Propulsive
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Cisapride
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Not studied. Cisapride has the potential to cause cardiac arrhythmias. Increased concentrations of cisapride may be possible.
(intestinal CYP3A4 enzyme inhibition)
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It is not recommended to co-administer OLYSIO with cisapride.
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Proton pump inhibitors
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Omeprazole
40 mg
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omeprazole AUC 1.21 (1.00-1.46) ↑
omeprazole Cmax 1.14 (0.93-1.39) ↑
omeprazole Cmin not studied
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No dose adjustment is required.
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Dexlansoprazole
Esomeprazole
Lansoprazole
Pantoprazole
Rabeprazole
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Not studied. No clinically relevant drug drug-interaction is expected.
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No dose adjustment is required.
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HCV PRODUCTS
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Antiviral
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Sofosbuvir2
400 mg once daily
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sofosbuvir AUC 3.16 (2.25-4.44) ↑
sofosbuvir Cmax 1.91 (1.26-2.90) ↑
sofosbuvir Cmin not studied
GS-331007 AUC 1.09 (0.87-1.37) ↔
GS-331007 Cmax 0.69 (0.52-0.93) ↓
GS-331007 Cmin not studied
simeprevir AUC 0.94 (0.67-1.33) ↔
simeprevir Cmax 0.96 (0.71-1.30) ↔
simeprevir Cmin not studied
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Increase in sofosbuvir exposure observed in the preliminary pharmacokinetic substudy is not clinically relevant.
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HERBAL PRODUCTS
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Milk thistle (Silybum marianum)
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Not studied. Increased plasma concentrations of simeprevir are expected.
(CYP3A4 enzyme inhibition)
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It is not recommended to co-administer OLYSIO with milk thistle.
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St John's wort (Hypericum perforatum)
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Not studied. Significantly decreased plasma concentrations of simeprevir are expected.
(CYP3A4 enzyme induction)
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It is not recommended to co-administer OLYSIO with products containing St John's wort as co-administration may result in loss of therapeutic effect of OLYSIO.
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HIV PRODUCTS
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Antiretroviral – CCR5 antagonist
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Maraviroc
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Not studied. No clinically relevant drug drug-interaction is expected.
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No dose adjustment is required for either drug when OLYSIO is co-administered with maraviroc.
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