Approval Date:
Revision Date:
Obiparib Tablets Instructions
Please read the instructions carefully and use under the guidance of your physician
For drugs used in combination with this product, please refer to the relevant drug label
Warning: risk of hepatitis B virus reactivation in HCV co-infected HBV patients
Clear evidence of current or prior hepatitis B virus (HBV) infection by testing in all patients before initiating treatment with this product + dasebuvir sodium. HBV reactivation has been reported in patients with HCV/HBV coinfection who were not receiving antiviral therapy for HBV when they were receiving or had completed direct antiviral therapy for HCV. Fulminant hepatitis, liver failure, and death have occurred in some cases. HCV treatment and post-treatment follow-up should be monitored for hepatitis episodes and HBV reactivation in HCV/HBV co-infected patients. Initiate appropriate management of HBV-infected patients based on clinical indications (see [Caution]).
[Drug Name]
Generic Name: Obiparib Tablets
Trade Name: Viekirax® Viekirax®
English name:Ombitasvir, Paritaprevir and Ritonavir Tablets
Hanyu Pinyin:Aobipali Pian
[Ingredients]
This product is a compound formulation, the components of which are: Obetavir12.5mg, paritaprevir75mg and ritonavir50mg.
[Traits]
This product is a pink oval film-coated tablet with “AV1″ engraved on one side ” on one side, which appears white or off-white after removing the coating.
This product is indicated in combination with other drugs for the treatment of chronic hepatitis C in adults (CHC). span style=”font-family:equinox”>) (see [Dosage], [Precautions], [Pharmacology and Toxicology], and [Clinical Trials]).
For hepatitis C virus (HCV) genotype-specific activity, see [Precautions], [Pharmacology and Toxicology] and [Clinical Trials].
[Specification]
Obitavir12.5mg per tablet, paritaprevir75mg and ritonavir50mg.
[dosage]
This product should be used under the guidance of a clinician experienced in the treatment of chronic hepatitis C.
Dosage
The recommended oral dose of this product is two tablets once daily (each dose12.5 mg/75 mg/50 mg) to be taken with food.
This product should be used in combination with the treatment ofHCVof other drugs in combination (see Table 1).
Table 1. Recommended Combination Drugs and Treatment Periods by Patient Population
Patient populationTherapeutic drugs*Treatment cycleGene 1bType span style=”font-family:Times New Roman”>,
No cirrhosis or compensated cirrhosisThis product+Dasebuvir sodium12weeksGene1aType =”font-family:Times New Roman”>,
No cirrhosisThis product+Dasebuvir sodium+ ribavirin*12weeksGene1aType =”font-family:Times New Roman”>,
Compensated cirrhosisThis product+Dasebuvir sodium+ ribavirin*24weeks (see [ Clinical Trials])Gene4Type /span>,
No cirrhosis or compensated cirrhosis, This product+Ribavirin12weeks* Note: Gene1type subtype unknown or genetic1mixed subtype infection patients should follow the genetic1atype dosing regimen. See the respective product insert for specific dosing instructions, including dose adjustments, for dasebuvir sodium and ribavirin.
missed dose
If a dose of this product is missed, the missed dose can be taken at the scheduled time of12hour of the prescribed dose. If more than 12hours have elapsed since the regular dosing time of this product, the missed dose should not be replaced and the patient should take the next dose at the scheduled dosing time. Patients should be informed that double doses should not be taken.
Special Populations
HIV-1Co-infection
Follow Table1dosing recommendations. ForHIVantiviral dosing recommendations, see [Precautions](HIVco-infected patients) and [Drug Interactions], see [Clinical Trials] for more information.
Liver Transplant Recipients
Recommend this product+dasebuvir sodium+ribavirin for the treatment of infectionsHCVgene1type of liver transplant recipients for a duration of 24weeks. It is recommended that this product+ ribavirin combination for the treatment of genes4patients with gentype 1 infection. A lower starting dose of ribavirin is appropriate. In post-liver transplant studies, ribavirin was administered on an individualized regimen, with most subjects being given at a dose of 600 to 800 mg daily (see [ Clinical Trials]). For dosing recommendations for calcium-regulated phosphatase inhibitors, see [Drug Interactions].
Geriatric Use
No dose adjustment is required for administration in elderly patients (see [Pharmacokinetics]).
Renal impairment
Patients with mild, moderate, or severe renal impairment or end-stage renal disease on dialysis do not require dose adjustment for this product (see [Pharmacokinetics]). Patients requiring ribavirin should refer to the ribavirin instruction sheet for information on use in patients with renal impairment.
Hepatic Impairment
Mild hepatic impairment
(Child-Pugh A grade) Child-Pugh A
Patients do not need to adjust the dose of this product to be administered. Combined with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment () (Child-Pugh C), or in patients with a relevant prior history of the above, is contraindicated (see [Contraindications], [Precautions], and [Pharmacokinetics]).
Pharmaceuticals for Children
This product is not yet available for18for minors under the age of 18 years.
Dosing method
Oral tablet. The patient should be instructed to swallow the entire tablet (i.e., the patient should not chew, break, or dissolve the tablet). This product should be taken with food to increase drug absorption without regard to the fat and calorie content of the food (see [Pharmacokinetics]).
Summary of Safety in Global Studies
In the global study, the safety summary was based on patients who received this product+dasebuvir sodium+/-ribavirin-treated2600 completed in more than subjects2Phase 2andPhase 3 clinical trial pooled data.
In patients receiving this product+ The most frequently reported adverse reactions in subjects treated with dasebuvir sodium+ ribavirin (20%or more subjects) were malaise and nausea. 0.2%(5/2,044) of subjects were permanently discontinued due to adverse reactions. 4.8%(99/2,044) subjects had their ribavirin dose reduced because of adverse reactions.
In subjects receiving this product+ The incidence of typical ribavirin-related adverse events (e.g., nausea, insomnia, anemia) was low in subjects treated with dasebuvir sodium (without ribavirin), and no patient (0/588) permanently discontinued treatment due to adverse reactions.
This product+daseb The safety profile of the combination of sodium dasebutide in subjects with compensated cirrhosis was similar to that of subjects without cirrhosis (except for the increased incidence of transient hyperbilirubinemia when combined with ribavirin).
List of adverse reactions
Table2The listed adverse reactions are related to this product+dasebuvir sodium+/-Adverse events with a causal relationship between the ribavirin combination that have at least a reasonable probability of a causal relationship with the study drug. Table2given in this product+The severity of the vast majority of adverse reactions occurring during treatment with the combination regimen of dasebuvir sodium was1Grade.
The following table lists adverse reactions by system organ classification and frequency of occurrence. Frequency is defined as follows: very common (≥1/10), common (≥1/100~<1/10), uncommon (≥1/1, 000 ~ <1/100), rare (≥1/10,000 ~ <1/1,000) or very rare (<1/10,000).
Table 2. Global study of this product+Dasabuvir sodium (+/-Ribavirin) Adverse Drug Reactions Occurring in Combination
FrequencyThis product+dasebuvir sodium+ribavirin *
N = 2,044This product+Dasebuvir sodium
N = 588 Blood and lymphatic system disorderscommonAnemia Psychiatricvery commonInsomnia Gastrointestinal Disordersvery commonNauseous
Dermal and subcutaneous tissue disordersVery commonItching Common itchingrareAngioedemaAngioedemaSystemic diseases and various reactions at the site of administrationvery commonLackluster, tired *The dataset includes 2periods and Phase 3trial in all infected genetic1types of Subjects, including subjects with cirrhosis.
Note: See Table 3 for laboratory abnormal values3.
Partial description of adverse reactions
Laboratory abnormal values
The variation of some laboratory parameters is shown in Table 3. For simplicity, present in side-by-side tables; however, direct comparisons should not be made across trials with different designs.
Tables 3. Selected laboratory abnormal values at the time of treatment
Lab parametersSAPPHIRE IandIIPEARL II, IIIandIVTURQUOISE II
(Subjects with cirrhosis)This product+Dasabuvir sodium+ Ribavirin
12weeks
N = 770
n (%)This product+Dasebuvir sodium
12week
N N = 509
n (%)This product+Dasebuvir sodium+ ribavirin
12 or 24weeks span style=”font-family:Times New Roman”>
N N = 380
n (%)ALT >5-20 × ULN*
(3levels)6/765(0.8%)1/509 (0.2%)4/380 (1.1%)>20 × ULN
(4levels)3/765(0.4%)02/380(0.5%)Hemoglobin <100-80 g/L (2level)41/765 (5.4%)030/380 (7.9%) <80-65 g/L(3levels)1/765(0.1%)03/380 (0.8%)<65 g/L (4level)001/380(0.3%)Total bilirubin >3-10 × ULN (3levels)19/765 (2.5%)2/509 (0.4%) 37/380 (9.7%)>10 × ULN (4levels) 1/765(0.1%)00*ULN: upper limit of normal value for each laboratory test Serum ALTelevated
Accept this product+dasebuvir sodium+/-in a pooled analysis of clinical trials of ribavirin treatment with1% of subjects whose serum after initiation of dosing ALTlevels above the upper limit of normal (ULN)5 times or more. Since female patients taking concomitant ethinyl estradiol-containing drugs have a ALTelevation incidence of26%, and therefore prohibits these drugs from being used with this product (+/-dasabuvir sodium) in combination with this product (dasabuvir sodium). No incidence of ALT elevation was observed when receiving other estrogen types commonly used in hormone replacement therapy (e.g., estradiol and conjugated estrogens) increased. ALTelevations are usually asymptomatic and usually occur initially during treatment. family:Times New Roman”>4weeks during treatment (mean time to20days, range:8-57days), with most events resolving with continued treatment. There were2 cases of patients who had a history of ALT because of ALT elevation and discontinued the product+dasebuvir sodium, including 1 patient treated with ethinyl estradiol. There were3patients who interrupted this product+dasabuvir sodium treatment1 to 7days, including 1patient treated with ethinyl estradiol. The vast majorityof the ALT elevations were transient and judged to be drug-related. The elevation of ALTis usually not associated with an elevation of bilirubin. Cirrhosis is not a risk factor forALT elevation (see [Caution]).
Elevated serum bilirubin
in the presence of elevated serum bilirubin after receiving this product+dasebuvir sodium+serum bilirubin (mainly indirect bilirubin) was observed in subjects treated with +ribavirin in a transient elevation, which was associated with inhibition of the bilirubin transport protein OATP1B1/1B3and ribavirin-induced hemolysis by paritaprevir. Bilirubin elevation occurred after initiation of treatment, peaked at study week 1, and usually recovered with continued treatment. Elevated bilirubin is not associated with elevated transaminases. Subjects not receiving ribavirin combination therapy had a lower incidence of indirect bilirubin elevation.
Liver transplant recipients
InfectionHCVhepatic transplant recipients (other than those receiving immunosuppressive therapy) receiving this product+dasabuvir sodium+The overall safety of ribavirin treatment is comparable toPhase 3 clinical trials receiving this product+dasebuvir sodium+Ribavirin-treated subjects were similar, although there was an increased incidence of some adverse reactions. 10 subjects (29.4%) had at least one post-baseline hemoglobin below10 g/dL. 10/34 cases of subjects (29.4%29.4%) had their ribavirin dose adjusted because of a decrease in hemoglobin,2.9%(1/34) subjects were suspended from ribavirin. Ribavirin dose adjustment had no effect onSVR rates. 5 subjects required administration of erythropoietin, and these patients received a starting dose of ribavirin daily1000-1200 mg. No subjects received blood transfusions.
HIV/HCVco-infected patients
Overall safety in HCV/HIV-1coinfected patients withHCVsole infected patients. 17 cases (27.0%) subjects had a transient increase in total bilirubin to >3×ULN (mainly indirect bilirubin); where15 subjects were treated with atazanavir. Of the subjects who developed hyperbilirubinemia, no patients had concomitant transaminase elevations.
Dermal reactions
In PEARL-II, PEARL-IIIandPEARL-IVin this product+dasebuvir sodium (7%) and this product+dasabuvir sodium in combination with ribavirin (10%) treated subjects reported rash-related events. InSAPPHIRE-I andSAPPHIRE-IIin 16% this product+ in subjects treated with dasebuvir sodium in combination with ribavirin and9% of subjects in the placebo-treated group reported skin reactions. In TURQUOISE-II, respectively, 18% and 24%accept12or24weeks of this product+daclatibuvir sodium in combination with ribavirin treatment reported skin reactions in subjects. The majority of events were mild in severity. There were no serious events or severe skin reactions such as Stevens Johnson syndrome (SJS), toxic epidermolysis bullosa (TEN), erythema multiforme (EM ) or drug rash with eosinophilia and systemic symptoms (DRESS), etc.
Post-marketing adverse reactions reported
Diseases of the hepatobiliary system: Receiving this product+/-dasebuvir sodium+/-Liver failure and liver failure have been reported in patients treated with ribavirin (see [Caution]). The frequency of these events is unknown.
Asia3Phase 3 Clinical Trial Safety Summary
Safety in Phase 3 clinical trials in Asia. The results were similar to those of the global study.
Pediatric Use
No data are available on the use of this product in 18year-old Security data for minors.
[Contraindicated]
It is contraindicated in cases of hypersensitivity to the raw materials or excipients of this product (see [Ingredients] Raw materials and excipients information).
Combined moderate hepatic impairment (Child-Pugh B) and severe hepatic impairment (Child-Pugh C), or a past history of such This product is contraindicated in patients (see [Pharmacokinetics]).
Estradiol-containing medications, such as most combination oral contraceptives or vaginal contraceptive rings, are contraindicated (see [Precautions] and [Drug Interactions]).
For highly dependentCYP3Acleared and where elevated blood levels are associated with serious adverse events, such drugs are contraindicated in combination with this product (see [Drug Interactions]). Examples are as follows:
CYP3A4Substrate:
Afrazosin hydrochloride
Aminoiodarone
Aspemidazole, terfenadine
Cisapride
Colchicine for patients with hepatic or renal impairment
Decadron
Ergotamine, Dihydroergotamine,
ergotoxine, methylergotoxine
Fusidic acid
Lovastatin, Simvastatin, Atorvastatin
Lurasidone
Oral midazolam, triazolam
Pimozide
Quetiapine
Quinidine
Renazine
Salmeterol
Sildenafil (when used to treat pulmonary hypertension)
Enzyme inducers:
Carbamazepine, phenytoin, phenobarbital
Efavirenz, nevirapine, etravirine
Ezalutamide
Mitrotan
Rifampicin
St. John’s Wort (Guan Ye Lianyi)
When this product (+/-dasabuvir sodium) is combined withCYP3A4potent inhibitors, it is expected to increase the paritaprevir plasma concentrations, so these drugs should not be used in combination with this product (see [Drug Interactions]). Examples of prohibitedCYP3A4potent inhibitors are as follows:
CYP3A4Inhibitors:
Cocostat
Indinavir, lopinavir/Ritonavir, saquinavir, tipranavir
Itraconazole, ketoconazole, posaconazole, voriconazole
Clarithromycin, Telithromycin
Conivaptan
If this product is used in combination with ribavirin, the contraindications to ribavirin also apply to the combination regimen. For contraindications to ribavirin, see the ribavirin instructions.
[Precautions]
General Notes
It is not recommended for use alone and must be used in combination with other drugs for the treatment of hepatitis C virus infection (see [Dosage] and [Pharmacology and Toxicology]).
Risk of hepatic decompensation and liver failure in patients with cirrhosis
In patients receiving this product+/-dasebuvir sodium (+/-ribavirin) in patients treated with this product, there have been reports of the development of hepatic decompensation and liver failure in postmarketing reports, including the need for liver transplantation or fatal outcomes. Of the patients who developed these serious outcomes, most had been diagnosed with advanced or decompensated cirrhosis prior to initiation of therapy. Although it is difficult to determine a causal relationship between the occurrence of this event and the patient being in an advanced stage of liver disease, the potential risk cannot be ruled out.
Combined moderate liver impairment (Child-Pugh B) and severe hepatic impairment (Child-Pugh C), or a past history of such This product is contraindicated in patients (see [DOSAGE], [ADVERSE REACTIONS] and [PHARMACOLOGY]).
For patients with cirrhosis:
Monitor clinical signs and symptoms of liver failure (e.g., ascites, hepatic encephalopathy. variceal bleeding).
baseline, initially treated4week and thereafter when clinically indicated, laboratory tests of liver function, including direct bilirubin, should be performed.
Patients presenting with evidence of hepatic decompensation discontinue therapy immediately.
ALTelevated
in this product+dasebuvir sodium (+/-ribavirin) in combination with this product in clinical trials, approximately1% of subjects (35/3039) showeda transient increase in ALT to the upper limit of normal. span>5fold or more. ALT elevations are usually asymptomatic and occur initially during treatment4weeks, without bilirubin elevation, and continuing this product+dasebuvir sodium (+/-ribavirin) therapy for about span>2weeks ALTsees a decline.
In the subgroup of subjects treated with ethinyl estradiol-containing (e.g., combination oral contraceptive pills or vaginal contraceptive rings) medications,ALTelevations were significantly more common (6/25 cases subjects) (see [Contraindications]). In contrast, in subjects receiving other types of estrogens (typically used in hormone replacement therapy, ie: oral and topical estrogens versus conjugated estrogens),ALT was similar to that observed in subjects not using estrogenic drugs (the incidence of elevated ALT in each group was approximately span>1%).
Before starting this product+ Prior to dasebuvir sodium combination, patients receiving ethinyl estradiol-containing medications (i.e., mostly combination oral contraceptives or vaginal contraceptive rings) must be switched to an alternative method of contraception (e.g., progestin-only or non-hormonal contraceptive methods) (see [Contraindications] and [Drug Interactions]).
Although the combination of this product with dasebuvir sodium caused ALTelevation is usually not clinically symptomatic, but patients should be instructed to watch for early signs of liver inflammation (e.g., malaise, weakness, loss of appetite, nausea, and vomiting) and to watch for later signs (e.g., jaundice and fecal discoloration) and to consult their physician immediately if such signs occur. Patients without cirrhosis do not need to follow the regular monitoring of liver enzymes for patients with cirrhosis (see above). Early discontinuation may lead to drug resistance, but the impact on subsequent therapy is not known.
Pregnancy and in combination with ribavirin
See [Pregnancy and Lactation]
When this product is used in combination with ribavirin, women of childbearing potential or the female partner of a male patient must use effective contraception. For more information, see [For Pregnant and Lactating Women] and Ribavirin Drug Formulary.
In combination with Tacrolimus, Sirolimus, and Everolimus
Since ritonavir has a significant effect onCYP3Ainhibition, and the combination of this product and dasebuvir sodium with systemically administered tacrolimus, sirolimus, or everolimus increases the blood levels of these immunosuppressive agents (see [Drug Interactions]). Serious and/ or life-threatening events have been observed with the combination of this product and dasebuvir sodium with systemically administered tacrolimus and are expected to occur with sirolimus and everolimus in combination with a similar risk.
Tacrolimus or sirolimus should be avoided in combination with this product and dasebuvir sodium unless the therapeutic benefit outweighs the potential risk. If tacrolimus or sirolimus is combined with this product and dasebuvir sodium, caution should be exercised and recommended dosing and monitoring methods can be found in [Drug Interactions]. Combination dosing with everolimus is not recommended because of the lack of appropriate specifications for dose adjustment.
After initiation of the combination with this product and dasebuvir sodium and throughout the combination period, whole blood concentrations of tacrolimus or sirolimus should be monitored, and the dose administered should be adjusted as needed and family:Times New Roman”>/ or dosing frequency should be adjusted as needed. Patients should be monitored frequently for any changes in renal function or adverse events associated with tacrolimus or sirolimus. For additional dosing and monitoring instructions, see the tacrolimus or sirolimus drug insert.
Genotype-specific activity
differentHCV genotypes and [Pharmacology and Toxicology] for virologic and clinical activity of different genotypes.
This product treats infections with genotype 2type,3type,type,5type and 6type patients There is no information on the effectiveness of the Therefore, it should not be used to treat patients infected with these genotypes.
with other HCVcombination of direct antivirals
This product+dasebuvir sodium+/-ribavirin have been demonstrated. In contrast, the combination of this product with other direct antiviral drugs is not available and is therefore not recommended.
Re-treatment
It has not been demonstrated that this product has any effect on patients who have received this or similar drugs (NS3/4Ainhibitors or NS5Ainhibitors). For cross-resistance refer to [pharmacology and toxicology].
with trans CYP3Ametabolized glucocorticoids (e.g., fluticasone) in combination
This product should be used with caution in combination with fluticasone or transCPY3A4CPY3A4metabolized by other glucocorticoids in combination . Combination with inhaled glucocorticoids metabolized byCYP3Amay increase systemic exposure to glucocorticoids. Cushing’s syndrome with secondary adrenal suppression has been reported with combination regimens containing ritonavir. The combination of this product with glucocorticoids, especially for long-term use, should be considered only if the potential benefit of systemic glucocorticoid therapy outweighs the risk (see [Drug Interactions]).
In combination with colchicine
This product has not been evaluated (+/-dasebuvir sodium) with colchicine. For combination therapy with this product (+/-dasebuvir sodium), it is recommended that patients with normal hepatic or renal function reduce the dose of colchicine administered or suspend colchicine therapy (see [Drug Interactions]). The combination of this product (+/-dasebuvir sodium) with colchicine is contraindicated in patients with hepatic or renal impairment (see [Contraindications] and [Drug Interactions]).
Combination with statins
Combination with simvastatin, lovastatin, and atorvastatin is prohibited (see [Contraindications] and [Drug Interactions]).
Risulvastatin
Co-administration with this product and dasabuvir sodium is expected to result in increased exposure to resulvastatin3 span style=”font-family:equinox”>fold or more. If a combination of Rosuvastatin is required during treatment, the maximum dose of Rosuvastatin should be adjusted to 5 mg/day (see [Drug Interactions], Table44. span>). The increase in exposure is not significant when resulvastatin is combined with this product (without dasabuvir sodium), and the maximum dose of resulvastatin under this combination regimen should be10 mg/day (see [Drug Interactions], Table 4).
pivastatin and fluvastatin
The interaction between this product and pitavastatin and fluvastatin is not known. Theoretically, co-administration with this product (+/-dasebuvir sodium) is expected to result in increased exposure to pitavastatin and fluvastatin. Suspension of pitavastatin/ fluvastatin is recommended while receiving this product. If a statin is necessary during treatment, switch to a lower dose of pravastatin/resvastatin (see [Drug Interactions], Table4).
HIV Treatment of co-infected patients
The combination contains a low dose of ritonavir for PIresistant antiretroviral therapy-naïveHIV co-infected patients may be treated with this product. Patients receiving antiretroviral therapy without virologic suppression should not receive this product.
InHIV co Drug interactions need to be carefully considered in infected populations (see [Drug Interactions], Table 4 for details).
Atazanavir in combination with this product+Dasabuvir sodium can be administered concurrently when used in combination. It is important to note that atazanavir is applied without the additional addition of ritonavir, as the once-daily administration of this product contains 100 mg of ritonavir. This combination regimen has an increased risk of hyperbilirubinemia (including scleral yellowing), especially when ribavirin is used as part of a hepatitis C regimen.
Dalunavir (at a dose of800 mg/day) for patients withoutPI pan-resistance (whose exposure dose is lower), may be given concurrently with this product in combination with dasabuvir sodium administration. Note that the addition of ritonavir to dalunavir applications is prohibited, as once-daily dosing of this product contains 100 mg of ritonavir.
Coadministration of other than atazanavir and darunavir is prohibitedHIVprotease inhibitors (e.g., indinavir, saquinavir, tipranavir, lopinavir/ritonavir (Vai) (see [Contraindication]).
Latelavir exposure increased substantially (2fold ). This combination regimen was used in a limited number of patients receiving 12to24weeks of treatment, no specific safety concerns were identified.
When rilpivirine was used with this product+Dasabuvir sodium in combination with a substantial increase in rilpivirine exposure (3fold), possibly secondary to prolonged QTinterval. If added to HIVprotease inhibitors (atazanavir, darunavir), rilpivirine exposure may even be further increased and therefore is not recommended Coadministration. Rilpivirine should be used with caution and should be monitored with repeated ECGs.
Coadministration of otherNNRTIs in addition to rilpivirine is contraindicated. -family:equiline”>(efavirenz, etravirine, and nevirapine) (see [Contraindications]).
Hepatitis B virus reactivation
Hepatitis B virus (HBV) reactivation has occurred during or after treatment with direct antiviral drugs. span>) reactivation has been reported in cases, some of which were lethal. All patients should be screened for HBV before starting treatment. HBV/HCVco-infected individuals presentHBVreactivation risk and therefore should be monitored and managed according to current clinical guidelines.
Pediatric Dosing
No data are available on this product for the treatment of 18 years of age or younger. Safety and validity data for minors.
Effects on the ability to drive and operate devices
Patients should be informed that malaise has been reported during the combination of this product, dasebuvir sodium, and ribavirin (see [Adverse Reactions]).
[For Pregnant and Lactating Women]
Females of childbearing age/Contraception for men and women
When this product is used in combination with ribavirin, female patients and female partners of male patients must take active measures to avoid conception. Ribavirin causes significant teratogenic and/ or embryotoxic effects in all animal species. Therefore, ribavirin is contraindicated in pregnant women and in male patients whose sexual partners are in pregnancy. For more information, please refer to the product insert of Ribavirin.
Female Patients: Women of childbearing potential should not be treated with ribavirin unless during and after completion of ribavirin treatmentfor 4months, unless they have been using effective contraception. Ethinylestradiol is contraindicated in combination with this product (see [Contraindications] and [Precautions]).
Male patients and their female partners: During and after ribavirin treatment7months, male patients or their female partners of childbearing age must use effective contraception.
Pregnancy
The data on the use of this product in women during pregnancy are extremely limited. Animal studies have shown that ombitasvir and paritaprevir/ritonavir are teratogenic (see [Pharmacology and Toxicology]). The potential risk to humans is unknown. It should not be used during pregnancy or by women of childbearing potential who are not using effective contraception.
Ribavirin should be contraindicated during pregnancy if ribavirin is used in combination with this product (see product insert for ribavirin).
Lactation
It is unclear whether ombitasvir/paritaprevir/and whether ritonavir and its metabolites are secreted via human milk. Available animal pharmacokinetic data indicate that the active substance and its metabolites can be detected in breast milk (see [Pharmacotoxicology]). This product may cause adverse reactions in breastfed infants, and the decision to discontinue breastfeeding or to discontinue treatment is based on the importance of the treatment to the mother. Patients receiving ribavirin combination therapy should also see the product insert for ribavirin.
Fertility
No data are available on the effect of this product on human fertility. No adverse effects on fertility have been found in animal studies. (See [Pharmacology and Toxicology]).
[Pediatric Use]
This product is not yet available for use in18for minors under the age of 18 years.
[Geriatric Use]
No dose adjustment is required for the administration of this product in elderly patients.
This product may be used with or without dasebuvir sodium. Interactions can occur when the two drugs are used in combination. (See [Pharmacokinetics]). Therefore, compound interactions must be considered when drugs are used in combination.
Pharmacodynamic interactions
Combination with enzyme inducers may increase the occurrence of adverse reactions andALTelevated risk (see Table 4). Combination with ethinyl estradiol may increase the risk of ALT elevation (see [Contraindications] and [Precautions]). See [Contraindications] for examples of prohibited enzyme inducers.
Pharmacokinetic interactions
Potential effects of this product on the pharmacokinetics of other drugs
In vivo drug interaction studies evaluated the net effect of combination (including ritonavir) therapy.
Following chapters describe the net effect of ritonavir in patients treated with this product (+/-dasebuvir sodium) affect specific transporter proteins and metabolic enzymes. Potential interactions with other drugs and dosing recommendations are shown in Table 4.
ByCYP3A4metabolized drugs
Ritonavir isCYP3Aa potent inhibitor of CYP3A. It (+/-dasabuvir sodium) is associated with the major transCYP3Ametabolized drugs may result in increased plasma concentrations of these drugs. It is contraindicated in combination with drugs that are highly dependent on CYP3Aclearance and can result in serious adverse events due to elevated blood concentrations. (See [Contraindications] and Table 4).
Drug interaction studies evaluated in which dose adjustments may be required for dosing and/or clinically monitoredCYP3Asubstrates include (see Table4): cyclosporine, tacrolimus, amlodipine, rilpivirine, and alprazolam. Other/ or clinically monitoredCYP3A4substrate examples include calcium channel blockers (e.g., nifedipine) and trazodone. Although buprenorphine and zolpidem are also metabolized by CYP3A, drug interaction studies have shown that when these drugs are combined with this product ( +/-dasabuvir sodium) in combination with this drug (), there is no need to adjust the dose of these drugs administered (see Table 4).
via the OATPfamily andOCT1transported drugs
Paritaprevir is a hepatic uptake of transporter proteinOATP1B1 and OATP1B3, and paritaprevir and ritonavir are inhibitors ofinhibitors of OATP2B1. Ritonavir is an in vitro inhibitor of OCT1, but the clinical relevance is unknown. This product (+/-dasabuvir sodium) is comparable to that used as aOATP1B1,OATP1B3, OATP2B1ororOCT1substrate drug combinations may increase plasma concentrations of these transporter protein substrates and may require dose adjustment/clinical monitoring. Such drugs include certain statins (see Table4), fexofenadine, repaglinide, and angiotensinIIreceptor antagonists (eg, valsartan).
drug interaction studies evaluated in OATP1B1/3substrates include pravastatin and rasuvastatin (see Table 4).
TranslocatedBCRPTransported drugs
In vivo, paritaprevir, ritonavir, and dasabuvir are BCRPinhibitors of BCRP. This product (+/-dasebuvir sodium) is similar to that used as aBCRPsubstrate may increase the plasma concentration of these transporter protein substrates and may require dose adjustment for administration/clinical monitoring. Such drugs include salazosulfapyridine, imatinib, and certain statins (see Table 4).
evaluated in drug interaction studiesBCRPsubstrates include resulvastatin (see Table 4).
Transcutaneous intestinalP-gptransported drugs
Although paritaprevir, ritonavir, and dasabuvir areP-gpin vitro inhibitors of P-gpbut this product was not observed in combination with dasabuvir sodiumP-gpSignificant changes in substrate (digoxin) exposure. However, the combination of digoxin with this product (not in combination with dasebuvir sodium) may result in increased digoxin plasma concentrations (see Table 4), and this product may lead to an increase in exposure to intestinal P-gpactivity-sensitive drugs (e.g., dabigatranide) with increased plasma exposure.
Transcutaneous glucuronidation (UGT1A1)-metabolized drugs
Paritaprevir, ombitasvir, and dasabuvir areUGT1A1inhibitors of UGT1A1. This product (+/-dasebuvir sodium) is associated with a major transUGT1A1metabolized drugs resulting in increased plasma concentrations of such drugs; routine clinical monitoring is recommended for drugs with narrow therapeutic indices (i.e.: levothyroxine). See Table 4 for recommendations related to raltegravir and buprenorphine that have been evaluated in drug interaction studies.
TranslationalCYP2C19metabolized drugs
with this product (+/-dasabuvir sodium) in combination may reduce the effect of drugs metabolized by CYP2C19 (e.g., lansoprazole, esomeprazole, ). span>S- mefetilone) exposure, which may require adjustment of the administered dose/clinical monitoring. The CYP2C19substrates evaluated in drug interaction studies include omeprazole and citalopram (see Table4).
ByCYP2C9metabolized drugs
with this product (+/-dasabuvir sodium) combination does not affect CYP2C9substrate (warfarin) exposure. No adjustment for CYP2C9other substrates (NSAIDs, e.g., ibuprofen; hypoglycemic agents, e.g., glimepiride, glipizide) at the dose administered.
AfterCYP2D6orCYP1A2metabolized drugs
with this product (+/- (dasebuvir sodium) co-administration does not affect CYP2D6 /CYP1A2substrate (duloxetine) exposure. Exposure to cyclobenzaprine (aCYP1A2substrate) was reduced after combination with this product. For otherCYP1A2substrates(e.g., ciprofloxacin, cyclobenzaprine, theophylline, and caffeine), clinical monitoring and dose adjustment of the administered dose may be required. No dose adjustment is anticipated forCYP2D6 substrates (e.g., desipramine, metoprolol, and dextromethorphan).
Drugs excreted via the kidney via transporter proteins
with tenofovir (OAT1substrate) without interaction could indicate that in vivo, ombitasvir, paritaprevir and ritonavir do not inhibit the organic anion transport protein (OAT1). In vitro studies have shown that at clinically relevant concentrations, ombitasvir, paritaprevir and ritonavir are not organic cationic transporter proteins (OCT2), the organic anion transporter protein (OAT3) or multidrug and toxin efflux transporter protein (MATE1andMATE2K) inhibitors.
Potential effects of other drugs on the pharmacokinetics of ombitasvir, paritaprevir, and dasebuvir
inhibitionof CYP3A4drugs
This product (+/- Dasebuvir sodium) in combination withCYP3Apotent inhibitors may increase blood levels of paritaprevir (see [Contraindications] and Table4).
Enzyme inducers
It is expected that this product (+dasebuvir sodium) in combination with drugs that are potent or moderately potent enzyme inducers decreases the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasebuvir, which in turn decreases the efficacy of these drugs. Contraindicated enzyme-inducing agents are listed in [Contraindications] and Table 4.
SuppressionCYP3A4 and transporter protein drugs
Palirevir is administered viaCYP34Amediated metabolism and biliary excretion for elimination (it is the hepatic transporter proteinOATP1B1, P-gpandandBCRPsubstrates). If this product is used with both CYP34Amedium-acting inhibitors and multiple transporter proteins (P-gp, BCRPand/orOATP1B1/ OATP1B3) inhibitors need to be used with caution in combination with drugs. These drugs (e.g., atazanavir+ritonavir, erythromycin, diltiazem, or verapamil) may lead to clinically relevant paritaprevir exposure increase.
Drugs that inhibit transporter proteins
P-gp, BCRP,OATP1B1and/orpotent inhibitors of OATP1B3 may increase exposure to paritaprevir. Inhibition of these transporter proteins is not expected to result in clinically relevant increases in ombitasvir and dasabuvir exposure.
Receiving vitamin Patients treated with Kantagonists
because of the lack of a specific treatment regimen in patients receiving this product (+/-dasebuvir sodium) may develop changes in liver function during treatment, so close monitoring of patients’ prothrombin time (INR).
Drug Interaction Studies
This product (+/-dasabuvir sodium) in combination with multiple drugs is recommended in Table 4.
While the patient is receiving this product (+/-dasabuvir sodium) treatment, consider adjusting the concomitant drug dose administered or giving appropriate clinical monitoring if the patient is receiving or starting to receive other drugs with which drug interactions may occur (Table 4).
If the product is used because of a combination with this product or this product+dasabuvir sodium, the concomitant drug dose should be readjusted when treatment with this product or this product+dasabuvir sodium is completed. dose.
For this product (+/- Dasebuvir sodium) and the least squares mean ratio (90%confidence interval) for the effect of concomitant drug isoconcentration are shown in Table 4.
Unless otherwise specified, when this product (+/-dasebuvir sodium) and the drugs listed in Table 4 are combined, the degree of interaction is similar (least squares mean ratio difference≤25%). Drug interactions were evaluated for the combination of this product+dasebuvir sodium with the following drugs: carbamazepine, furosemide, zolpidem , darunavir (twice daily), darunavir (evening dosing), atazanavir (evening dosing), or rilpivirine, abacavir/lamivudine, dolutegravir, metformin, sulfamethoxazole/methotrexate, cyclobenzaprine, cariprodol, hydrocodone/acetaminophen or diazepam. Therefore, for these drugs, extrapolation to a regimen in which this product is not combined with dasebuvir sodium can be made based on the results of drug interactions with this product and dosing recommendations.
Indicate with arrows the exposure to ombitasvir, paritaprevir, dasabuvir, and concomitant drugs (CmaxandAUC) direction of change ( ↑=increases20% more,↓ =down20%above,↔ =no change or change below20%). This table is not a complete list.
Table 4. Between this product (+/-dasebuvir sodium) and other drugs Interactions
Medications/possible interactions
Mechanisms of actionCombined medicationsEffectCmaxAUCCminClinical Reviewα1adrenoceptor antagonistAfrazosin
Mechanism: ritonavir inhibitsCYP3AThis product (+/-Dasebuvir sodium)not studied, expected:
↑AfrazosinProhibited association (see [taboo]Aminosalicylic acidLyuzosulfapyridine
Mechanism: inhibition by paritaprevir, ritonavir and dasebuvirBCRPThis product (+/-Dasabuvir sodium)Not studied, expected:
↑LyuzosulfapyridineWhen salazosulfapyridine is combined with this product (+/-dasabuvir sodium) should be used with caution. Angiotensin receptor antagonistsValsartan
Closartan
Candesartan
Mechanism: Palirevir inhibitsCYP3A4 and/or “font-family:Times New Roman”>OATP1BThis product (+/-Dasabuvir sodium)Not studied, expected:
↑Valsartan
↑ Closartan
↑ Candesartan
When this product (+/-dasebuvir sodium) is used in combination with angiotensin receptor inhibitors, clinical monitoring and lowering the dose of angiotensin receptor inhibitors administered is recommended. Anti-Angina/Anti-arrhythmic drugsAmiodarone
Decadron
Quinidine
Renazine
Mechanism: ritonavir inhibitsCYP3A4 This product (+/-Dasebuvir sodium) Not studied,
Expected:
↑ Amiodarone
↑ Decadron
↑ Quinidine
↑RenazineProhibited association (see [taboo])
Digoxin
0.5 mgSingle dose Drug
Mechanism: Paritaprevir ritonavir and dasebuvir inhibitP-gpThis product+Dasabuvir sodium↔ Digoxin1.15
(1.04-1.27)1.16
(1.09-1.23)1.01
(0.97-1.05)While no digoxin dose adjustment is necessary, monitoring of digoxin serum concentrations is recommended. ↔ ↔ =”font-family:equals”>Obitavir
1.03
(0.97-1.10)1.00
(0.98-1.03)0.99
(0.96-1.02)↔ Palirevir0.92
(0.80-1.06)0.94
(0.81-1.08)0.92
(0.82-1.02)↔ Dasebvir0.99
(0.92-1.07)0.97
(0.91-1.02)0.99
(0.92-1.07)This product is not co-administered with dasabuvir sodium↑ Digoxin1.58
(1.43-1.73)1.36
(1.21-1.54)1.24
(1.07-1.43)Recommend digoxin dose reduction30-50%; recommend monitoring digoxin serum concentrations. ↔ ObjectiveThe magnitude of the interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↔ Palirevirantibiotics (systemic)Clarithromycin
Telelithromycin
Mechanism: Clarithromycin and ritonavir inhibitCYP3A4/P-gpThis product (+/-Dasabuvir sodium)Not studied, expected:
↑clarithromycin
↑Telelithromycin
↑ Paritaprevir
↑ DasabuvirProhibited association (see [taboo]Erythromycin
Mechanism: erythromycin, paritaprevir, ritonavir, and dasebuvir inhibitCYP3A4/P-gpThis product
(+/-Dasebuvir sodium)Not studied, expected:
↑Erythromycin
↑ Paritaprevir
↑ DasabuvirThis product (+/-dasebuvir sodium) in combination with erythromycin may result in increased concentrations of erythromycin and paritaprevir and is recommended with caution. Fusidic acid
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑Fusidic acidProhibited association (see [taboo]Sulfamethoxazole, Methotrexate
800/160 mg
Twice daily
Mechanism: increased exposure to dasebuvir may be due to meperidine inhibitionCYP2C8This product+Dasabuvir sodium↑Sulfamethoxazole1.21(1.15-1.28)1.17(1.14-1.20)1.15(1.10-1.20)This product in combination with or without dasebuvir sodium does not require dose adjustment for administration. ↑Methotrexate1.17(1.12-1.22)1.22(1.18-1.26)1.25(1.19-1.31)↔ Obitasvir0.88(0.83-0.94)0.85(0.80-0.90)NA↓ Paritaprevir0.78(0.61-1.01)0.87(0.72-1.06)NA↑ Dasebwe1.15(1.02-1.31)1.33(1.23-1.44)NAThis product is not combined with dasebuvir sodiumNot studied: expected to be associated with this product+dasabuvir sodium administration produces similar results to those observed. Anti-cancer drugsEnzalutamide
Mitrotan
Mechanism: enzalutamide or mitotane inducesCYP3A4This product (+/-Dasebuvir sodium)Not studied, expected:
↓Ombitasvir
↓ Paritaprevir
↓ DasabuvirProhibited association (see [taboo])
Imatinib
Mechanism: inhibition by paritaprevir, ritonavir and dasebuvirBCRPThis product (+/-Dasabuvir sodium)Not studied, expected:
↑Imatinib
Recommendation for clinical monitoring, imatinib administered at lower dosesAnticoagulantsWarfarin
5 mg single dose /span>
and other vitaminK antagonistsThis product+Dasebuvir sodium↔ R-Warfarin1.05
(0.95-1.17)0.88
(0.81-0.95)0.94
(0.84-1.05)While the pharmacokinetics of warfarin are not expected to change, the combination with all vitaminKClose monitoring of INRis recommended when antagonists are combined. Because hepatic function changes occur with this product±dasebuvir sodium treatment. ↔ S-Warfalin0.96
(0.85-1.08)0.88
(0.81-0.96)0.95
(0.88-1.02)↔ Obitavir0.94
(0.89-1.00)0.96
(0.93-1.00)0.98
(0.95-1.02)↔ Palirevir0.98
(0.82-1.18)1.07
(0.89-1.27)0.96
(0.85-1.09)↔ Dasebvir0.97
(0.89-1.06)0.98
(0.91-1.06)1.03
(0.94-1.13)This product (not combined with dasebuvir sodium)↔ R-WarfarinThe magnitude of the interaction is similar to that observed for this product+dasebuvir sodium Similar results were observed with the combination. ↔ S-Warfalin↔ Palirevir↔ ObitavirObitavirDabigatransate
Mechanism: Paritaprevir and ritonavir inhibit intestinalP-gp. This product (+/-Dasebuvir sodium)not studied, expected:
↑Dabigatranate
This product (not in combination with dasabuvir sodium) may increase plasma concentrations of dabigatranate. Use with caution. AnticonvulsantsCarbamazepine
Once daily, each time 200mg, followed by 200mg twice daily
Mechanism: carbamazepine-inducedCYP3A4This product+Dasebuvir sodium↔Carbamazepine1.10
(1.07-1.14)1.17
(1.13-1.22)1.35
(1.27-1.45)Prohibited association (see [taboo] ↓Carbamazepine10, 11- Epoxy0.84
(0.82-0.87)0.75
(0.73-0.77)0.57
(0.54-0.61)↓ Obitavir0.69
(0.61-0.78)0.69
(0.64-0.74)NA↓ Palirevir0.34
(0.25-0.48)0.30
(0.23-0.38)NA↓ Dasebvir0.45
(0.41-0.50)0.30
(0.28-0.33)NAThis product (not in combination with dasebuvir sodium)Not studied: expected with this product+dasabuvir sodium in combination, similar effects were observed. Phenobarbital
Mechanism: phenobarbital inducesCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↓ Ombitasvir
↓ Paritaprevir
↓ DasabuvirProhibited association (see [taboo]Phenytoin
Mechanism: phenytoin-induced CYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↓ Ombitasvir
↓ Paritaprevir
↓ DasabuvirProhibited association (see [taboo])
S-Mefentoin
Mechanism: ritonavir-inducedCYP2C19This product (+/-Dasebuvir sodium)Not studied, expected:
↓ S-Mefentoin
Clinical monitoring may be required and adjustmentsS-Mefenacetin dosing. AntidepressantsEscitalopram
10 mg, single dose medicationThis product+Dasebuvir sodium↔Escitalopram1.00
(0.96-1.05)0.87
(0.80-0.95)NANo need to adjust escitalopram No Escitalopram dose adjustment is required. ↑S-Demethylcitalopram1.15
(1.10-1.21)1.36
(1.03-1.80)NA↔ Obitabavir1.09
(1.01-1.18)1.02
(1.00-1.05)0.97
(0.92-1.02)↔ Palirevir1.12
(0.88-1.43)0.98
(0.85-1.14)0.71
(0.56-0.89)↔ Dasebwe1.10
(0.95-1.27)1.01
(0.93-1.10)0.89
(0.79-1.00)This product
(not combined with dasebuvir sodium)↓CitalopramThe magnitude of the interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↔ S-Demethylcitalopram1.17
(1.08-1.26)1.07
(1.01-1.13)NA↔ Obitavir
amplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium↔ PalirevirDuloxetine
60 mg, single dose medicationThis product+Dasebuvir sodium↓ Duloxetine0.79
(0.67-0.94)0.75
(0.67-0.83)NANo duloxetine dose adjustment required.
No need to adjust this product (+ /-dasebuvir sodium) dose. ↔ Objective0.98
(0.88-1.08)1.00
(0.95-1.06)1.01
(0.96-1.06)↓ Paritaprevir0.79
(0.53-1.16)0.83
(0.62-1.10)0.77
(0.65-0.91)↔ Dasebwe0.94
(0.81-1.09)0.92
(0.81-1.04)0.88
(0.76-1.01)This product
(not combined with dasebuvir sodium)↔DuloxetineThe magnitude of the interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↔ ObjectiveInteraction The magnitude was similar to that observed with the combination of this product+dasebuvir sodium. ↔ Palirevir1.07
(0.63-1.81)0.96
(0.70-1.32)0.93
(0.76-1.14)Trazodone:
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑TrazodoneTrazodone should be used with caution, and a lower trazodone dose may be considered. Anti-diuretic hormoneKoenigvartan
Mechanism:
Conivaptan and paritaprevir/Ritonavir/Ombitasvir suppressionCYP3A4/P-gpThis product (+/-dasebuvir sodium)Not studied, expected:
↑Conivaptan
↑ Paritaprevir
↑ DasabuvirProhibited association (see [taboo]AntifungalsKetoconazole once daily at 400mg
Mechanism: ketoconazole and this product inhibitCYP3A4/P-gpThis product+Dasabuvir sodium↑Ketoconazole1.15
(1.09-1.21)2.17
(2.05-2.29)NAProhibited association (see [taboo])
↔ Objective0.98
(0.90-1.06)1.17
(1.11-1.24)NA↑ Palirevir1.37
(1.11-1.69)1.98
(1.63-2.42)NA↑ Dasebwe1.16
(1.03-1.32)1.42
(1.26-1.59)NAThis product (not in combination with dasebuvir sodium)↑ =”font-family:equinox”>KetoconazoleAmplitude of interaction with this product+ similar to that observed with the combination of dasebuvir sodium. ↑ ObitabixInteraction The magnitude was similar to that observed with the combination of this product+dasebuvir sodium. ↑ Palirevir1.72
(1.32-2.26)2.16
(1.76-2.66)NAItraconazole, posaconazole
Mechanism: Itraconazole, posaconazole and paritaprevir/Ritonavir/Obitavir inhibitionCYP3A4 and/orP-gpThis product+dasebuvir sodium
Not studied, expected:
↑Itraconazole =”font-family:Times New Roman”>
↑Posaconazole
↑ Paritaprevir
↑ DasabuvirLinkage is prohibited (see [taboo]This product (not combined with dasabuvir sodium)Voriconazole
Mechanism: ritonavir inducesCYP2C19, inhibition ofCYP3A4This product (+/-dasebuvir sodium)Not studied, expected:CYP2C19fast metabolizing patients:
↓Voriconazole
↑ Paritaprevir
↑ Dasabuvir
Not studied, expected: CYP2C19Patients with slow metabolism:
↑Voriconazole
↑ Dasabuvir
↑ ParitaprevirProhibited association (see [taboo]Anti-gout drugsColchicine
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑ ColchicineIf you need this product (+/-dasebuvir sodium) therapy, it is recommended to reduce the colchicine dose or suspend colchicine therapy in patients with normal hepatic or renal function. Colchicine in combination with this product (+/-dasebuvir sodium) is contraindicated in patients with renal or hepatic impairment (see [Contraindications] and [Precautions])dasebuvir sodium). span>AntihistaminesAspemidazole
Tefenadine
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑Aspemidazole/TefenadineProhibited association (see [taboo]FexofenadineFexofenadine /span>
Mechanism: Paritaprevir inhibitsOATP1B1This product (+/-Dasebuvir sodium)Not studied, expected:
↑FexofenadineWhen this product (+/- dasabuvir sodium) should be used with caution in combination with fexofenadine. Lipid-lowering medicationsGiffirozil
Twice daily, each 600 mg
Mechanism: The increase in dasebuvir exposure is due toCYP2C8inhibition; the increase in paritaprevir exposure may be due to gefirozil inhibitionOATP1B1 Palirevir/Ritonavir+Dasebuvir sodium↑ =”font-family:equinox”>Palirevir1.21 (0.94-1.57)1.38
(1.18-1.61)NAProhibited in combination with this product+Dasabuvir sodium (see [Contraindication]↑ Dasebwe2.01
(1.71-2.38)11.25
(9.05-13.99)NAThis product
(not combined with dasebuvir sodium)not studied;
No interaction is expected when this product (not in combination with dasebuvir sodium) is administered in combination with gemfibrozil. No need to adjust the dose of gemfibrozil or to adjust the dose of this product. Anti-mycobacterial drugsRifampicin:
Mechanism: Rifampin induces CYP3A4. This product (+/-Dasebuvir sodium)not studied, expected:
↓ Ombitasvir
↓ Paritaprevir
↓ DasabuvirProhibited association (see [taboo]Anti-psychotic drugsLurasidone
Pimozide
Quetiapine
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑Pimozide
↑Quetiapine
↑LurasidoneProhibited association (see [taboo]Anti-platelet drugsTegretol
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑TegretolProhibited association (see [taboo]Biguanide oral hypoglycemic drugsMetformin
500 mg
Single doseThis product+dasebuvir sodium↓ Metformin0.77(0.71-0.83)0.90(0.84-0.97)NAThis product (+/-dasebuvir sodium) in combination with metformin, no dose adjustment of metformin administration is required. ↔Obitabavir0.92(0.87-0.98)1.01(0.97-1.05)1.01(0.98-1.04)↓ Palirevir0.63(0.44-0.91)0.80(0.61-1.03)1.22(1.13-1.31)↔ Dasebvir0.83(0.74-0.93)0.86(0.78-0.94)0.95(0.84-1.07)This product
(not combined with dasebuvir sodium)not studied: similar effects to those observed with this product+dasebuvir sodium administration are expected. Calcium channel blockersAminochlodipine
5 mg, single dose
Mechanism: ritonavir inhibitsCYP3A4This product+Dasebuvir sodium↑Aminochlodipine1.26
(1.11-1.44)2.57
(2.31-2.86)NAreduce amlodipine dose by 50%and monitor the clinical outcome of patients. ↔ Objective1.00
(0.95-1.06)1.00
(0.97-1.04)1.00(0.97-1.04)↓ Palirevir0.77
(0.64-0.94)0.78
(0.68-0.88)0.88(0.80-0.95)↔ Dasebvir1.05
(0.97-1.14)1.01
(0.96-1.06)0.95(0.89-1.01)This product (not in combination with dasebuvir sodium)Unresearched:
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Diltiazem, Verapamil
Mechanism: Inhibition of CYP3A4/P-gpThis product (+/-dasebuvir sodium)Not studied, expected:
↑Diltiazem, Vera Palmi
↑ Paritaprevir
↑/↔ DasabuvirDasabuvir Because of the anticipated increased exposure to paritaprevir, caution is warranted.
When used with this product (+/- dasebuvir sodium), a lower dose of calcium channel blocker with clinical monitoring is recommended. Nifedipine
Mechanism: inhibition of CYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑ NifedipineWhen used with this product (+/ dasebuvir sodium), a lower dose of calcium channel blocker with clinical monitoring is recommended. The PillEstradiol/Norgestrel
Once daily, each time 0.035/0.25 mg
Mechanism: possibly due to paritaprevir, ombitasvir
and dasebuvir inhibitionUGTThis product (+/-dasebuvir sodium)↔Estradiol1.16
(0.90-1.50)1.06
(0.96-1.17)1.12
(0.94-1.33)Oral contraceptives containing ethinyl estradiol should be contraindicated (see [Contraindications])Metabolites of ethinylestradiol:↑ Kynurenine2.26
(1.91-2.67)2.54
(2.09-3.09)2.93
(2.39-3.57)↑Norgestrol2.01
(1.77-2.29)2.60
(2.30-2.95)3.11
(2.51-3.85)↔ Obitasvir1.05
(0.81-1.35)0.97
(0.81-1.15)1.00(0.88- 1.12)↓Palirevir0.70
(0.40-1.21)0.66
(0.42-1.04)0.87(0.67-1.14)↓ Dasebvir0.51
(0.22-1.18)0.48
(0.23-1.02)0.53(0.30- 0.95)Kynurenine (progestogen-only drug)
Once daily, each time 0.35 mgThis product+Dasebuvir sodium↔Kynurenine0.83
(0.69-1.01)0.91
(0.76-1.09)0.85
(0.64-1.13)No need to adjust the dose of norethindrone or this product (+/-dasebuvir sodium) administered. ↔ Objective1.00
(0.93-1.08)0.99
(0.94-1.04)0.97
(0.90-1.03)↑ Paritaprevir1.24
(0.95-1.62)1.23
(0.96-1.57)1.43(1.13-1.80)↔ Dasebvir1.01
(0.90-1.14)0.96
(0.85-1.09)0.95
(0.80-1.13)This product (not combined with dasebuvir sodium) Not studied
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. DiureticsFurosemide
20 mg, single dose medication
Mechanism: Possible because paritaprevir, ombitasvir, and dasebuvir inhibitUGT1A1This product+Dasabuvir Sodium↑ Furosemide1.42
(1.17-1.72)1.08
(1.00-1.17)NAMonitoring of patient clinical outcomes; may require up to a 50% reduction in furosemide dose.
No need to adjust this product (+ dasebuvir sodium) at the dose administered↔ Obitabavir1.14
(1.03-1.26)1.07
(1.01-1.12)1.12(1.08-1.16)↔ Palirevir0.93
(0.63-1.36)0.92
(0.70-1.21)1.26(1.16-1.38)↔ Dasebwe1.12
(0.96-1.31)1.09
(0.96-1.23)1.06(0.98-1.14)This product (not combined with dasebuvir sodium)Unresearched
Expected to be associated with this product+similar effects to those observed with dasebuvir sodium administration. Ergot alkaloidsErgotamine
Dimethylergotamine
Ergonovine
Methylergotoxine
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑ Ergot derivativesProhibited association (see [taboo]Glucocorticoids (inhaled)Fluticasone
Mechanism: Ritonavir inhibitionCYP3A4
This product (+/-Dasebuvir sodium)not studied, expected:
↑ FluticasoneCoadministration with fluticasone may increase systemic exposure to fluticasone. The combination of this product with glucocorticoids should only be considered if the potential benefit of systemic glucocorticoid therapy (especially long-term therapy) outweighs the risk. Gastrointestinal Drugs (Motility Drugs)Sisabili
Mechanism: Ritonavir inhibitionCYP3A4This product (+/-dasebuvir sodium)Not studied, expected:
↑ Sisabri
Prohibited association (see [taboo]HCVAntiviralsSofosbuvir,
400 mg
once daily
Mechanism: paritaprevir, ritonavir and dasebuvir inhibitionBCRPandP-gpThis product+Dasebuvir Sodium↑Sophosbuvir1.61
(1.38-1.88)2.12
(1.91-2.37)NAThis product is used in combination or not in combination with dasebuvir sodium and sofosbuvir without adjustment of the dose of sofosbuvir administered. ↑ GS-3310071.02
(0.90-1.16)1.27
(1.14-1.42)NA↔ Obitasvir0.93
(0.84-1.03)0.93
(0.87-0.99)0.92
(0.88-0.96)↔ Palirevir0.81
(0.65-1.01)0.85
(0.71-1.01)0.82
(0.67-1.01)↔ Dasebwe1.09
(0.98-1.22)1.02
(0.95-1.10)0.85
(0.76-0.95)This product (not combined with dasebuvir sodium)Interaction The magnitude was similar to that observed in the combined treatment with this product+dasebuvir sodium. Chinese herbsSt. John’s Wort
(Cross-leaved coneflower)
Mechanism: Conophyllum contagiosum inducesCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↓ Dasebvir
↓ Ombitasvir
↓ ParitaprevirProhibited association (see [taboo]HIVAntivirals: protease inhibitors
For the treatment ofHIVcoinfected patients for an overview (including a discussion of the different antiretroviral regimens that may be used), see [Caution](HIVtreatment of co-infected patients). Azanavir
Once daily, each time 300 mg(administered simultaneously)
Mechanism: The increase in paritaprevir exposure may be attributable to atazanavir inhibitionOATP1B1/B3andCYP3AThis product+Dasebuvir sodium↔Azanavir0.91
(0.84-0.99)1.01
(0.93-1.10)0.90
(0.81-1.01)When atazanavir is used in combination with this product and dasabuvir sodium (not in combination with ritonavir), the recommended dose of atazanavir is300 mg, atazanavir must be administered concurrently with this product + dasabuvir sodium. The ritonavir dose in this product enhances the pharmacokinetics of atazanavir.
No need to adjust this product +dose of dasebuvir sodium administered.
Not recommended
Atazanavir co-administered with this product (not in combination with dasabuvir sodium) regimen-(↑ paritaprevir).
Atazanavir with this product + Dasabuvir sodium in combination can result in elevated bilirubin levels, particularly when ribavirin is used as part of a hepatitis C combination regimen, see [Precautions] and [Adverse Reactions]. ↓ Obitabavir0.77
(0.70-0.85)0.83
(0.74-0.94)0.89
(0.78-1.02)↑ Paritaprevir1.46
(1.06-1.99)1.94
(1.34-2.81)3.26
(2.06-5.16)↔ DasebweDasebwe
0.83
(0.71-0.96)0.82
(0.71-0.94)0.79
(0.66-0.94)This product (not in combination with dasebuvir sodium)↔ AzanavirThe magnitude of the interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↑ Paritaprevir2.74
(1.76-4.27)2.87
(2.08-3.97)3.71
(2.87-4.79)↔ Obitasviramplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. Azanavir/Ritonavir
Once daily, each time 300/100 mg
(interval12hour dosing)
Mechanism: The increase in paritaprevir exposure may be attributable to atazanavir inhibitionOATP1B1/B3andCYP3A, and the inhibition of CYP3A by additional doses of ritonavirThis product+Dasebuvir sodium↔Azanavir1.02
(0.92-1.13)1.19
(1.11-1.28)1.68
(1.44-1.95)↔ Obitasvir0.83
(0.72-0.96)0.90
(0.78-1.02)1.00
(0.89-1.13)↑ Paritaprevir2.19
(1.61-2.98)3.16
(2.40-4.17)11.95
(8.94-15.98)↔ Dasebwe0.81
(0.73-0.91)0.81
(0.71-0.92)0.80
(0.65-0.98)This product (not in combination with dasebuvir sodium)Unresearched.
Expected to be associated with this product+similar effects to those observed with dasebuvir sodium administration. Darunavir
Once daily, each time 800 mg(administered simultaneously)
Mechanism: unknownthis product+dasebuvir sodium↓Darunavir 0.92
(0.87-0.98)0.76
(0.71-0.82)0.52
(0.47-0.58)Because this ritonavir-containing dose enhances the pharmacokinetics of darunavir, when darunavir is administered concurrently with this product+dasabuvir sodium, the recommended dose of darunavir is 800 mg once daily (no additional ritonavir co-administration) ) in the absence of PI pan-resistance (i.e., lack of darunavir-associatedRAMs), this regimen may be used, see [Caution].
No need to adjust this product+. /span>dose of dasebuvir sodium administered.
Dalunavir is not recommended with this product + dasabuvir sodium in combination with this productPI. Patients with pan-drug resistance.
Darunavir is not recommended+ this regimen (not in combination with dasabuvir sodium) (↑ paritaprevir) ↔Obitavir0.86
(0.77-0.95)0.86
(0.79-0.94)0.87
(0.82-0.92)↑Palirevir1.54
(1.14-2.09)1.29
(1.04-1.61)1.30
(1.09-1.54)↔ Dasebvir1.10
(0.88-1.37)0.94
(0.78-1.14)0.90
(0.76-1.06)This product (not in combination with dasebuvir sodium)↔Darunavir0.99
(0.92-1.08)0. 92
(0.84-1.00)0.74
(0.63-0.88)↔Obitaviramplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↑Palirevir2.09
(1.35-3.24)1.94
(1.36-2.75)1.85
(1.41-2.42)Darunavir/ Ritonavir
Twice daily, each 600/100 mg
Mechanism: unknownThis product+dasebuvir sodium ↔Darunavir0.87
(0.79-0.96)0.80
(0.74-0.86)0.57
(0.48-0.67)↓ Obitavir0.76
(0.65-0.88)0.73
(0.66-0.80)0.73
(0.64-0.83)↓ Paritaprevir0.70
(0.43-1.12)0.59
(0.44-0.79)0.83
(0.69-1.01)↓ Dasebvir0.84
(0.67-1.05)0.73
(0.62-0.86)0.54
(0.49-0.61)This product (not combined with dasebuvir sodium) Not studied.
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Darunavir/Ritonavir
Once daily, each time 800/100 mg
(interval12hour dosing)
Mechanism: unknownThis product+dasebuvir sodium ↑Darunavir0.79
(0.70-0.90)1.34
(1.25-1.43)0.54
(0.48-0.62)↔Obitavir0.87
(0.82-0.93)0.87
(0.81-0.93)0.87
(0.80-0.95)↓ Paritaprevir0.70
(0.50-0.99)0.81
(0.60-1.09)1.59
(1.23-2.05)↓ Dasebvir0.75
(0.64-0.88)0.72
(0.64-0.82)0.65
(0.58-0.72)This product (not combined with dasebuvir sodium) Not studied:
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Lopinavir/Ritonavir
Twice daily, each 400/100 mg1
Mechanism: the increase in paritaprevir exposure may be attributable to the effect of lopinavir onCYP3A/inhibition of efflux transport proteins, and the effect of high doses of ritonavir. This product+Dasebuvir sodium↔Lopinavir0.87
(0.76-0.99)0.94
(0.81-1.10)1.15
(0.93-1.42)Prohibited association (see [taboo])↔ Obitavir1.14
(1.01-1.28)1.17
(1.07-1.28)1.24
(1.14-1.34)↑Paritaprevir2.04
(1.30-3.20)2.17
(1.63-2.89)2.36
(1.00-5.55)↔ Dasebvir0.99
(0.75-1.31)0.93
(0.75-1.15)0.68
(0.57-0.80)This product (not in combination with dasebuvir sodium)↔LopinavirThe magnitude of the interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↑Obitabixmagnitude of interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↑Palirevir4.76
(3.54-6.39)6.10
(4.30-8.67)12.33
(7.30-20.84)Indinavir
Saquinavir
Tilaprevir
Mechanism: protease inhibitor inhibitsCYP3A4This product (+/-dasebuvir sodium)Not studied, expected
↑ ParitaprevirProhibited association (see [taboo]HIVAntivirals: non-nucleoside reverse transcriptase inhibitorsRipivirine 2
once daily, each time25mg in the morning with food.
Mechanism: ritonavir inhibitsCYP3A4This product+Dasabuvir sodium↑ Ripivirine2.55
(2.08-3.12)3.25
(2.80-3.77)3.62
(3.12-4.21)This product+dasebuvir sodium in combination with rilpivirine (once daily) is indicated only for Patients with a knownQTinterval without prolongation and should not be combined with rilpivirine that causesQTinterval prolongation and should not be combined with drugs that cause interval prolongation. If combined, repeated monitoring of ECG is required, see [Caution].
No need to adjust this product (+ /-dasebuvir sodium) at the dose administered. ↔ Objective1.11
(1.02-1.20)1.09
(1.04-1.14)1.05
(1.01-1.08)↑ Paritaprevir
1.30
(0.94-1.81)1.23
(0.93-1.64)0.95
(0.84-1.07)↔ Dasebvir1.18
(1.02-1.37)1.17
(0.99-1.38)1.10
(0.89-1.37)This product (not combined with dasebuvir sodium) Not studied:
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Efavirenz/Entriptabine/tenofovir
once daily600/300/200 mg
Mechanism: possible efavirenz inductionCYP3A4This product (+/-dasebuvir sodium)Efavirenz (enzyme inducer)-based regimens with paritaprevir Ritonavir + dasabuvir sodium combination leads to ALT elevation, thus leading to early termination of the study. Prohibited in combination with efavirenz (see [Contraindication]Nevirapine
Etravirine
This product (+/-Dasebuvir sodium)not studied, expected:
↓ Ombitasvir
↓ Paritaprevir
↓ DasabuvirProhibited association (see [taboo]HIVantivirals: integrase strand transfer inhibitorsDotilaprevir
50 mg daily Once
Mechanism: probably due to inhibition of paritaprevir, dasabuvir, and ombitasvirUGT1A1and ritonavir inhibitionCYP3A4This product+Dasebuvir sodium↑ Dotilaprevir1.22
(1.15-1.29)1.38(1.30-1.47)1.36(1.19-1.55)When used with this product (+/-dasabuvir sodium), no dose adjustment of dolutegravir is required↔Objective0.96(0.89-1.03)0.95(0.90-1.00)0.92(0.87-0.98)↔ Palirevir0.89(0.69-1.14)0.84(0.67-1.04)0.66(0.59-0.75)↔Dasebwe1.01(0.92-1.11)0.98(0.92-1.05)0.92(0.85-0.99)This product (not in combination with dasebuvir sodium)Not studied.
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Ratilavir
Twice daily, each 400mg
Mechanism: paritaprevir, ombitasvir
and dasabuvir inhibitionUGT1A1This product+Dasebuvir sodium↑ Ratilavir2.33
(1.66-3.27)2.34
(1.70-3.24)2.00
(1.17-3.42)No need to adjust the dose of raltegravir or this product (+/-dasabuvir sodium) administered . During drug combination, observation of dasebuvir, paritaprevir, and ombitasvir exposure had no clinically relevant changes (based on results compared with historical data). This product (not in combination with dasebuvir sodium)↑ Raltegravir1.22
(0.78-1.89)1.20
(0.74-1.95)1.13
(0.51-2.51)No clinically relevant changes in exposure to dasabuvir, paritaprevir, and ombitasvir were observed during the drug combination (based on results compared with historical data). HIVAntivirals: nucleoside inhibitorsAbacavir /Lamivudine
600/300 mg
once dailyThis product+dasebuvir sodium↔ Abacavir0.87(0.78-0.98)0.94(0.90-0.99)NAwith this product (+/-dasebuvir sodium) in combination with this product (no need to adjust the dose of abacavir or lamivudine administration. ↓ Lamivudine0.78(0.72-0.84)0.88(0.82-0.93)1.29(1.05-1.58)↔Obitavir0.82(0.76-0.89)0.91(0.87-0.95)0.92(0.88-0.96)↔ Palirevir0.84(0.69-1.02)0.82(0.70-0.97)0.73(0.63-0.85)↔Dasebwe0.94(0.86-1.03)0.91(0.86-0.96)0.95(0.88-1.02)This product (not in combination with dasebuvir sodium) Not studied: expected to be associated with this product+dasebuvir administration to produce similar effects to those observed with this product. Entragitabine/Tenofovir
Tenofovir once daily, each time 200mg/once daily, each time300mgThis product+Dasebuvir sodium↔ Entricitabine1.05
(1.00-1.12)1.07
(1.00-1.14)1.09
(1.01-1.17)No adjustment needed for emtricitabine/Tenofovir
and this product (+/-dasabuvir sodium) at the Dose administered. ↔Tenofovir1.07
(0.93-1.24)1.13
(1.07-1.20)1.24
(1.13-1.36)↔ Obitavir0.89
(0.81-0.97)0.99
(0.93-1.05)0.97
(0.90-1.04)↓ Paritaprevir
0.68
(0.42-1.11)0.84
(0.59-1.17)1.06
(0.83-1.35)↔ DasebweDasebwe
0.85
(0.74-0.98)0.85
(0.75-0.96)0.85
(0.73-0.98)This product (not in combination with dasebuvir sodium)↔EntragitabineThe magnitude of the interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↔Tenofovir
0.80
(0.71-0.90)1.01
(0.96-1.07)1.13
(1.06-1.21)↔ Obitabavir
amplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↔ Paritaprevir1.02
(0.63-1.64)1.04
(0.74-1.47)1.09
(0.88-1.35)HIVAntivirals: pharmacokinetic enhancersTherapeutic regimens with cobicistat
Mechanism: Inhibition by comparisostatCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑ Ombitasvir
↑ Paritaprevir
↑ DasabuvirProhibited association (see [taboo]HMG CoAreductase inhibitorRisulvastatin
once daily 5mg.
Mechanism: Paritaprevir inhibitsOATP1B; paritaprevir, ritonavir and dasabuvir inhibitBCRPThis product+Dasebuvir Sodium↑Risulvastatin7.13
(5.11-9.96)2.59
(2.09-3.21)0.59
(0.51-0.69)The maximum daily dose of Rosuvastatin should be5 mg (see [Precautions]) .
No need to adjust this product +. /span>dose of dasebuvir sodium administered. ↔ Objective0.92
(0.82-1.04)0.89
(0.83-0.95)0.88
(0.83-0.94)↑ Paritaprevir1.59
(1.13-2.23)1.52
(1.23-1.90)1.43
(1.22-1.68)↔ DasebweDasebwe
1.07
(0.92-1.24)1.08
(0.92-1.26)1.15
(1.05-1.25)This product (not in combination with dasebuvir sodium)↑Risulvastatin2.61
(2.01-3.39)1.33
(1.14-1.56)0.65
(0.57-0.74)
The maximum daily dose of resulvastatin is10 mg (see [Precautions]) without adjustment of the dose of this product to be administered. ↔ Obitabavirmagnitude of interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↑ Paritaprevir1.40
(1.12-1.74)1.22
(1.05-1.41)1.06
(0.85-1.32)Pravastatin
Once daily, each time 10mg
Mechanism: Paritaprevir inhibitsOATP1B1This product+ Dasebuvir sodium↑Pravastatin
1.37
(1.11-1.69)1.82
(1.60-2.08)NAPravastatin dose reduction50%.
No need to adjust this product (+ /-dasebuvir sodium) at the dose administered. ↔ Objective0.95
(0.89-1.02)0.89
(0.83-0.95)0.94
(0.89-0.99)↔ Dasebwe
1.00
(0.87-1.14)0.96
(0.85-1.09)1.03
(0.91-1.15)↔ Paritaprevir
0.96
(0.69-1.32)1.13
(0.92-1.38)1.39
(1.21-1.59)This product (not in combination with dasebuvir sodium)↑Pravastatin
amplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↔ Obitavirmagnitude of interaction was similar to that observed with the combination of this product+dasebuvir sodium. ↑ Palirevir
1.44
(1.15-1.81)1.33
(1.09-1.62)1.28
(0.83-1.96)Fluvastatin
Mechanism: Paritaprevir inhibitsOATP1B/BCRP
pivastatin
Mechanism:
Paritrevir inhibition OATP1B
This product (+/-Dasebuvir sodium) Not studied, expected:
↑Fluvastatin
↑pivastatinNot recommended in combination with fluvastatin and pitavastatin (see [Precautions])
Temporary discontinuation of fluvastatin and pitavastatin is recommended during the treatment period of this product. If statin therapy is required during the treatment period, it may be necessary to switch to a lower dose of pravastatin or rasulvastatin. Lovastatin
Simvastatin
Atorvastatin
Mechanism: CYP3A4/OATP1Bis inhibited
This product (+/-Dasebuvir sodium)not studied, expected:
↑lovastatin, simvastatin, atorvastatinProhibited association (see [taboo]ImmunosuppressantsCyclosporine
Once daily, each time 30 mg3
Mechanism: effect on cyclosporine may be due to ritonavir inhibitionCYP3A4. The increase in paritaprevir exposure may be due to cyclosporine inhibitionOATP/BCRP /P-gpThis product+dasebuvir sodium↑ Cyclosporine1.01
(0.85-1.20)5.82
(4.73-7.14)15.8
(13.8-18.09)When cyclosporine is initiated in combination with this product, give one-fifth of the total daily dose of cyclosporine, administered once daily. Monitor cyclosporine concentrations simultaneously and adjust the dose and/ or frequency of administration if needed.
No need to adjust this product (+ /-dasebuvir sodium) at the dose administered. ↔ Objective0.99
(0.92-1.07)1.08
(1.05-1.11)1.15
(1.08-1.23)↑ Paritaprevir1.44
(1.16-1.78)1.72
(1.49-1.99)1.85
(1.58-2.18)↓ Dasebvir
0.66
(0.58-0.75)0.70
(0.65-0.76)0.76
(0.71-0.82)This product (not in combination with dasebuvir sodium)↑ Cyclosporine
0.83
(0.72-0.94)4.28
(3.66-5.01)12.8
(10.6-15.6)↔ Obitasviramplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↑ Palirevir
1.39
(1.10-1.75)1.46
(1.29-1.64)1.18
(1.08-1.30)Everolimus
0.75 mg,. Single dose
Mechanism: the effect on everolimus is because ritonavir inhibits CYP3A4This product+Dasebuvir sodium↑Evimox4.74
(4.29-5.25)27.12
(24.5-30.1)16.10
(14.5-17.9)4The combination of this product with everolimus is not recommended because it results in a significant increase in exposure to everolimus and there are no appropriate specifications for dose adjustment (see [Precautions])↔ Obitavir 0.99
(0.95-1.03)1.02
(0.99-1.05)1.02
(0.99-1.06)↔ Paritaprevir 1.22
(1.03-1.43)1.26
(1.07-1.49)1.06
(0.97-1.16)↔ Dasebvay 1.03
(0.90-1.18)1.08
(0.98-1.20)1.14
(1.05-1.23)This product (not combined with dasebuvir sodium)Unresearched:
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Sirolimus
0.5 mg, single Administration5
Mechanism: the effect on sirolimus is due to ritonavir inhibition CYP3A4This product+Dasebuvir sodium↑Sirolimus6.40
(5.34-7.68)38.0
(31.5-45.8)19.6
(16.7-22.9)6Cirolimus is not recommended in combination with this product unless the therapeutic benefit outweighs the risk (see [Precautions]). If sirolimus is used in combination with this product+dasabuvir sodium, sirolimus gives family:Times New Roman”>0.2 mgtwice weekly (every3or4days, given on the same two days of the week). The patient’s sirolimus blood levels should be monitored every 4 – 7days until continuous3times until the blood trough concentration of sirolimus has reached steady state. Adjust the dose and/ or frequency of administration of sirolimus as needed.
In this product+. span>dasabuvir sodium treatment ends5 days after treatment with this product, it should be The sirolimus dose and frequency of administration prior to receiving this product should be reintroduced, and sirolimus blood levels should be routinely monitored. ↔ Objective1.03
(0.93-1.15)1.02
(0.96-1.09)1.05
(0.98-1.12)↔ Palirevir1.18
(0.91-1.54)1.19
(0.97-1.46)1.16
(1.00-1.34)↔ Dasabuvir sodium1.04
(0.89-1.22)1.07
(0.95-1.22)1.13
(1.01-1.25)This product (not combined with dasebuvir sodium)Unresearched:
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Tacrolimus
2 mg, single dose 4
Mechanism: the effect on tacrolimus is due to ritonavir inhibitionCYP3A4This product+Dasabuvir Sodium↑Tacrolimus3.99
(3.21-4.97)57.1
(45.5-71.7)16.6
(13.0-21.2)The combination of tacrolimus with obiparib is not recommended unless the benefit of treatment outweighs the risk (see [Precautions]).
If tacrolimus is given in combination with this product and dasebuvir sodium, tacrolimus should not be given on the same day that this product and dasebuvir sodium are started. Beginning the day after initiation of treatment with this product and dasebuvir sodium, a reduced dose of tacrolimus should be readministered based on the tacrolimus blood level. The recommended dose of tacrolimus is every7days0.5 mg.
Tacrolimus concentrations in whole blood should be monitored after initiation of the combination with this product and dasebuvir sodium and throughout the combined dosing period, and dosing should be adjusted as needed Dose and/ or frequency of administration should be adjusted as needed. After the end of treatment with this product+dasebuvir sodium, the appropriate dose and dosing frequency should be given based on the blood level of tacrolimus. ↔ Objective0.93
(0.88-0.99)0.94
(0.89-0.98)0.94
(0.91-0.96)↓ Paritaprevir0.57
(0.42-0.78)0.66
(0.54-0.81)0.73
(0.66-0.80)↔ Dasebwe0.85
(0.73-0.98)0.90
(0.80-1.02)1.01
(0.91-1.11)This product (not in combination with dasebuvir sodium)↑Tacrolimus4.27
(3.49-5.22)85.8
(67.9-108)24.6
(19.7-30.8)↔ Obitabavir
amplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↓ PalirevirInhaledbetareceptor agonistsSalmeterol
Mechanism: ritonavir inhibitsCYP3A4This product (+/-Dasebuvir sodium)not studied, expected:
↑ SalmeterolCombination is prohibited (see [taboo]). Proinsulin secretagoguesRiglinide
Mechanism: inhibition by paritaprevirOATP1B1This product (+/-Dasebuvir sodium)Not studied, expected:
↑ RiglinideWhen used with this product (+/-dasebuvir sodium), caution is required and a reduction in the dose of repaglinide may be necessary. Muscarinic drugsCalipto
250 mg
Single dose
Mechanism: ritonavir-inducedCYP2A19This product+Dasebuvir sodium↓Calipto0.54
(0.47-0.63)0.62(0.55-0.70)NANo adjustment of the dose of cariprodol administered is required; if clinically indicated, the dose administered may be increased. ↔Objective0.98(0.92-1.04)0.95(0.92-0.97)0.96(0.92-0.99)↔ Paritaprevir0.88(0.75-1.03)0.96(0.85-1.08)1.14(1.02-1.27)↔ Dasebvir0.96(0.91-1.01)1.02(0.97-1.07)1.00(0.92-1.10)This product (not combined with dasebuvir sodium)not studied and is expected to be similar to that observed with this product+dasebuvir sodium administration the results produced similar effects. Cyclobenzalin
5 mg
Single dose
Mechanism: reduction may be due to ritonavir-inducedCYP1A2This product+Dasabuvir sodium↓Cyclobenzalin0.68
(0.61-0.75)0.60(0.53-0.68)NANo adjustment of the dose of cyclobenzaprine administered is required; if clinically indicated, the dose administered may be increased. ↔Obitavir0.98(0.92-1.04)1.00(0.97-1.03)1.01(0.98-1.04)↔ Palirevir1.14(0.99-1.32) 1.13(1.00-1.28) 1.13(1.01-1.25) ↔Dasebwe0.98(0.90-1.07)1.01(0.96-1.06)1.13(1.07-1.18)This product (not in combination with dasebuvir sodium) Not studied, expected to be associated with this product+dasebuvir sodium administration to produce similar results to those observed with this product. Narcotic analgesics Acetaminophen (fixed dose hydrocodone/acetaminophen)
300 mg, single administeredThis product+Dasebuvir sodium↔ Acetamides
Kibitol1.02
(0.89-1.18)1.17
(1.09-1.26)NAand this product (+/-dasebuvir sodium) in combination No dose adjustment of acetaminophen administration is required when acetaminophen is administered. ↔Obitabavir1.01(0.93-1.10)0.97(0.93-1.02)0.93(0.90-0.97)↔ Palirevir1.01(0.80-1.27)1.03(0.89-1.18)1.10(0.97-1.26)↔Dasebwe1.13(1.01-1.26)1.12(1.05-1.19)1.16(1.08-1.25)This product (not combined with dasebuvir sodium)Not studied, expected to be associated with this product+similar effects to those observed with dasebuvir sodium administration. Hydrocodone (fixed dose of hydrocodone/acetaminophen)
5 mg, single dose
Mechanism: ritonavir inhibitsCYP3A4This product+Dasebuvir sodium↑ Hydrocodone1.27
(1.14-1.40)1.90
(1.72-2.10)NAwith this product (+/-dasebuvir sodium), the dose of hydrocodone administered in combination with this product (+/-dasebuvir sodium) should be reduced50% and monitored clinically. Changes in ombitasvir, paritaprevir, and dasabuvir sodium Same as above for co-administered acetaminophen. This product (not combined with dasebuvir sodium)Not studied, expected to be associated with this product+dasabuvir sodium administration to produce similar results to those observed. OpioidsMethadone
once daily, each time 20-120mg8This product+Dasabuvir Sodium↔ R-Methadone1.04
(0.98-1.11)1.05
(0.98-1.11)0.94
(0.87-1.01)No need to adjust the dose of methadone and this product (+/-dasebuvir sodium) administered. ↔ S-Methadone0.99
(0.91-1.08)0.99
(0.89-1.09)0.86
(0.76-0.96)↔ParitaprevirOmbitasvir/ Dasebuvir sodium (based on cross-sectional study comparison)This product (not in combination with dasebuvir sodium) amplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. Buprenorphine/Naloxone
once daily, each time4 -24 mg/1-6 mg 8
Mechanism: ritonavir inhibitsCYP3A4, paritaprevir, ombitasvir and dasabuvir inhibitUGTThis product+Dasebuvir Sodium↑Buprenorphine2.18
(1.78-2.68)2.07
(1.78-2.40)3.12
(2.29-4.27)No need to adjust for buprenorphine/Naloxone and this product (+/-dasabuvir sodium). ↑ Deprenyl Buprenorphine2.07
(1.42-3.01)1.84
(1.30-2.60)2.10
(1.49-2.97)↑Naloxone1.18
(0.81-1.73)1.28
(0.92-1.79)NA↔ Obitavirparitaprevir/ Dasebuvir (based on cross-sectional study comparison)this product (not in combination with dasebuvir sodium)
↑ Buprenorphine1.19
(1.01-1.40)1.51
(1.27-1.78)1.65
(1.30-2.08)↑ Deprenyl Buprenorphineamplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↔ Naloxone↔ Obitavir/Paritaprevir
(based on comparative results according to cross-sectional studies)Phosphodiesterase-() PDE-5)inhibitorsSildenafil (for pulmonary hypertension)
Mechanism: ritonavir inhibitsCYP3A4This product (+/-dasebuvir sodium)
Not studied, expected:
↑SildenafilProhibited association (see [taboo]Proton pump inhibitorsOmeprazole
Once daily, each time 40 mg
Mechanism: ritonavir inducesCYP2C19This product+Dasebuvir sodium↓Omeprazole0.62
(0.48-0.80)0.62
(0.51-0.75)NAHigher doses of omeprazole may be given if clinically indicated.
No need to adjust this product (+ /-dasebuvir sodium) at the dose administered. ↔ Obitavir1.02
(0.95-1.09)1.05
(0.98-1.12)1.04
(0.98-1.11)↔ Palirevir1.19
(1.04-1.36)1.18
(1.03-1.37)0.92
(0.76-1.12)↔ Dasebwe1.13
(1.03-1.25)1.08
(0.98-1.20)1.05
(0.93-1.19)This product (not in combination with dasebuvir sodium)↓Omeprazole0.48
(0.29-0.78)0.46
(0.27-0.77)NA↔ Obitasvir
amplitude of interaction with this product+similar to that observed with the combination of dasebuvir sodium. ↔ Paritapreviresomeprazole
Lansoprazole
Mechanism: ritonavir-inducedCYP2C19This product+/-Dasebuvir Sodiumnot studied, expected:
↓Esomeprazole. LansoprazoleIf clinically indicated, higher doses of esomeprazole may be given/Lansoprazole. Sedatives/hypnoticsZolpidem
5 mg, single dose This product+Dasebuvir sodium↔ Zolpidem
0.94
(0.76-1.16)0.95
(0.74-1.23)NANo need to adjust zolpidem dosing.
No adjustment of this product is required (+ /-dasebuvir sodium) at the dose administered. ↔ Obitavir1.07
(1.00-1.15)1.03
(1.00-1.07)1.04
(1.00-1.08)↓ Paritaprevir0.63
(0.46-0.86)0.68
(0.55-0.85)1.23
(1.10-1.38)↔ Dasebwe
0.93
(0.84-1.03)0.95
(0.84-1.08)0.92
(0.83-1.01)This product (not combined with dasebuvir sodium) Not studied.
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Alprazolam
0.5 mg, single Administration
Mechanism: ritonavir inhibitsCYP3A4This product+Dasebuvir sodium↑Alprazolam1.09
(1.03-1.15)1.34
(1.15-1.55)NAPatient clinical monitoring is recommended. Depending on clinical response, alprazolam dose reduction may be considered.
No adjustment of this product is required (+ /-dasebuvir sodium) at the dose administered. ↔ Obitavir0.98
(0.93-1.04)1.00
(0.96-1.04)0.98
(0.93-1.04)↔ Palirevir0.91
(0.64-1.31)0.96
(0.73-1.27)1.12
(1.02-1.23)↔ Dasebwe
0.93
(0.83-1.04)0.98
(0.87-1.11)1.00
(0.87-1.15)This product (not combined with dasebuvir sodium) Not studied.
Expected to be associated with this product+similar results to those observed with dasebuvir sodium administration. Oral Midazolam
Triazolam(24weeks)TURQUOISE III
(Open style=”font-family:Times New Roman”>)60GT1bThis product+dasebuvir sodium (12weeks)in all7weeks. in all clinical trials, the dose of this product was administered once daily at 25 mg/150 mg/100 mg, and dasebuvir was administered at a dose of 250 mg twice daily. For patients treated with ribavirin, the ribavirin dose for patients weighing less than 75 kg is daily1000mg for patients weighing equal to or greater than 75 kg the dose of ribavirin for patients is1200 mg daily.
Continuous virologic response (SVR) is a measure of 3stage studyHCV cure rate as defined as the primary endpoint at the end of treatment12 =”font-family:isochrone”>week (SVR12)HCV RNAis undetectable or not quantifiable. The treatment period for each trial is fixed and independent of the patient’sHCV RNAlevel (no treatment guidance based on response is required). During the clinical trial,HCV RNA was measured usingCOBAS TaqMan HCVassay (2.0version), which uses the High Pure system. High Puresystems have a lower limit of quantification (LLOQ) of 25 IU/mL.
Clinical trials in primary care adult patients
SAPPHIRE-I – genetic1type, primary, without cirrhosis
Trial design: randomized, global multicenter, double-blind, placebo-controlled
Treatment regimen: this product+dasebuvir sodium+ribavirin (dose administered based on patient weight) for treatment12weeks
Patients treated (N=631) with a median age of 52 years (range:18 to 70years old);54.5%patients were male;5.4%patients were black;15.2%patients had a history of depression or bipolar disorder;79.1%of patients had baselineHCV RNAlevels of at least800,000 IU/mL;15.4%of patients developed fibrosis in the confluent area (F2), 8.7%of patients developed bridge-like fibrosis ( F3);67.7% of patients infected withHCV gene1atype;32.3%32.3%of patients were infected with gene1btype.
table6. SAPPHIRE-Istudy in genetic1type primed patientsSVR12
Results of treatmentThis product+dasebuvir sodium+ribavirin therapy12 “font-family:isoline”>weekn/N%95% CITotalSVR12Rate456/47396.494.7, 98.1HCVGene1atype308/32295.793.4, 97.9HCV Gene1btype148/ 15198.095.8, 100.0not obtainedSVR12patient results Occurrence during treatmentVFa 1/4730.2 Recurrence7/4631.5 Otherb9/4731.9 Requires confirmation that the patient achievedHCV RNA < 25 IU/mLand then reappearwith HCV RNA ≥ 25 IU/mL, confirming HCV RNA levels compared to lowest value1 log10 IU/mL, or treatment with at least6weeks afterHCV RNA “font-family:equinox”>still≥ 25 IU/mL
Other outcomes include early discontinuation not due to virologic failure (inSVR12time window for deletionHCV RNAdetection values)
NoHCV Gene1bpatients with virologic failure on treatment, 1caseHCVgene 1bPatients with HCVtype 1 relapse.
PEARL-III -genetic1btype, primary
, without cirrhosis
Trial design: randomized, global multicenter, double-blind, controlled trial
Treatment regimen: this product +dasebuvir sodium +/-ribavirin (dose administered based on patient weight) treatment12weeks.
Patients treated (N=419) with a median age of 50 years (range:19 to 70years old);45.8%patients were male;4.8%patients were black;9.3%patients had a history of depression or bipolar disorder;73.3%patients had baselineHCV RNAlevels of at least800,000 IU/mL;20.3%of patients developed fibrosis in the confluent area (F2) and10.0%patients with bridge-like fibrosis (F3).
Table 7. PEARL IIIstudy in genetic1btype primed patients withSVR12
Treatment resultsThis product+dasebuvir sodium treatment12weeks + Ribavirin- Ribavirinn/N%95% CIn/N%95% CI SVR12Rate209/21099.598.6, 100.0209/20910098.2, 100.0not obtainedSVR12patient resultsDuring treatmentVF1/2100.5 0/2090 Recurrence0/2100/2100 0/2090 Other0/2100 0/2090 PEARL-IV-Gene 1atype, primary, without cirrhosis
Trial design: randomized, global multicenter, double-blind, controlled trial
Treatment regimen: this product +dasebuvir sodium +/-ribavirin (dose administered based on patient weight) treatment12weeks
Patients treated (N=305) with a median age of 54years (range:19 to 70years old);65.2%patients were male;11.8%patients were black;20.7%patients had a history of depression or bipolar disorder;86.6%of patients had baselineHCV RNAlevels of at least800,000 IU/mL;18.4% of patients developed fibrosis in the confluent area (F2) and17.7%patients developed bridge-like fibrosis (F3).
Table 8. PEARL IVstudy in genetically1apatients with first treatment of typeSVR12
Treatment resultsThis product+ Dasebuvir sodium treatment12weeks+ Ribavirin-ribavirinn/N%95% CI n/N%95% CI SVR12rate97/10097.093.7, 100.0185/20590.286.2, 94.3Not obtainedSVR12patient resultsDuring treatmentVF1/1001.0 6/2052.9 Recurrence1/981.0 10/1945.2 other1/1001.0 4/2052.0 Polyethylene glycol interferon+clinical trial of ribavirin in treated adult patients
SAPPHIRE-II -Gene11Gene = “font-family:equals; text-decoration:underline”>, pegIFN+ribavirin treated without cirrhosis
Trial design: randomized, global multicenter, double-blind, placebo-controlled
Dose administered: this product+dasebuvir sodium+ribavirin (dose administered based on patient weight) in combination therapy12weeks
Patients treated (N=394) with a median age of 54years (range:19 to 71years old);49.0%patients were non-responders to previouspegIFN/RBVtreatment;21.8%of patients were previouslypegIFN/RBVtreatment partial responders;29.2%patients were relapsed patients on previouspegIFN/RBVtreatment;57.6%of patients were male; 8.1%of patients were black;20.6%patients had a history of depression or bipolar disorder;87.1%patients had a baselineHCV RNAlevels of at least800,000 IU/mL; 17.8% of patients developed fibrosis in the confluent area (F2), 14.5% of patients developed pontine fibrosis (F3);58.4% of patients were infected withHCVgene1atype;41.4%of patients were infectedHCVgene1btype dye.
Table 9. SAPPHIRE-IIstudy in gene1type, pegylated interferon+ ribavirin in patients treated withSVR12
Treatment resultsThis product+Dasabuvir sodium+Ribavirin
Treatment12weeksn/N%95% CITotalSVR12rate 286/29796.394.1, 98.4HCVgene1atype166/173 96.093.0, 98.9previouslypegIFN/RBVTreatment non-responders83/8795.495.491.0, 99.8previouslypegIFN/RBVtreatment of partial responders36/36100100.0, 100.0previously pegIFN/RBVTreatment relapse patients47/5094.087.4, 100.0 HCV Gene1btype119/123 96.793.6, 99.9previouspegIFN/RBVTreatment non-responders56/5994.989.3, 100.0previouslypegIFN/RBVtreatment of partial responders 28/28100100.0, 100.0previouslypegIFN/RBVtreated relapsed patients35/3697.291.9, 100.0not obtainedSVR12patient results During treatmentVF0/2970 Recurrence7/2932.4 Other4/2971.3 NoneHCVgenetic1bpatients with virologic type 1 in treatment failure, 2 cases of HCVHCVgene1bpatients presenting with relapse.
PEARL-II – Gene1bType, pegIFN+RBVtreated without cirrhosis
Trial design: randomized, global multicenter, open trial
Treatment regimen: this product +dasebuvir sodium +/-ribavirin (dose administered based on patient weight) treatment12weeks
Patients treated (N=179) with a median age of 57years (range:26 to 70years old);35.2%patients were previouspegIFN/RBVnon-responders;28.5% of patients were priorpegIFN/RBVtreatment partial responders;36.3%patients were relapsed patients with previouspegIFN/RBVtreatment;54.2%of patients were male;3.9% patients were black;12.8%patients had history of depression or bipolar disorder;87.7%patients had a baselineHCV RNAlevels of at least800,000 IU/mL; 17.9% of patients developed fibrosis in the confluent area (F2), 14.0% of patients developed pontine fibrosis (F3).
Table10. PEARL IIstudy in gene1btype of pegylated interferon+ ribavirin-treated patientsSVR12
Treatment resultsThis product+dasebuvir sodium treatment12weeks + ribavirin- Ribavirinn/N%95% CIn/N%95% CITotalSVR12rate86/8897.794.6, 100.091/9110095.9, 100.0previouslypegIFN/RBVtreatment non-responders30/3196.890.6, 100.032/3210089.3, 100.0previously. /span>pegIFN/RBVTreatment of partial responders24/2596.088.3, 100.026/2610087.1, 100.0previouslypegIFN/RBVTreatment relapse patients32/3210089.3, 100.033/3310089.6, 100.0Not obtainedSVR12patient results During treatmentVF 0/880 0/910 Recurrence0/880 0/910 Other2/882.3 0/91 0 Replacement clinical trial in patients with stage I cirrhosis
TURQUOISE-II-genetic1type, primary orpegIFN+RBVtreated, with compensated cirrhosis
Trial design: randomized, global multicenter, open trial
Treatment regimen: this product+dasebuvir sodium+ribavirin (dose administered based on patient weight) for treatment12weeks or24week
Patients treated (N=380) with a median age of 58 years (range:21 to 71years old);42.1%patients were first-time patients;36.1%patients were previouspegIFN/RBVnon-responders; 8.2%of patients were previouslypegIFN/RBVtreatment partial responders;13.7%of patients were priorpegIFN/RBVtreatment relapse patients;70.3%patients were male;3.2%patients were black. 14.7%of patients had platelet counts less than90 x 109/L;49.7%patients with albumin levels less than40g/L;86.1% of patients at baseline HCV RNAlevels of at least800,000 IU/mL; 24.7%of patients had a history of depression or bipolar disorder;68.7%patients were infected withHCVgenetic1atype; 31.3%of patients were infected with the gene 1bType.
Table11. gene1type with compensated cirrhosis in primary orpegIFN/RBVin treated patients withSVR12
Treatment resultsThis product+ Dasebuvir sodium+ribavirin 12week24weeksn/N%CIan/N %CIaTotalSVR12rate191/20891.887.6, 96.1166/17296.593.4, 99.6HCV gene1aType124/14088.683.3, 93.8115/12195.091.2, 98.9Primary patients59/6492.2 53/5694.6 previouspegIFN/RBVtreatment non-responders 40/5080.0 39/4292.9
Table12shows the relapse rate in patients with GT1a cirrhosis according to different baseline laboratory test values.
Table12. TURQUOISE-IIstudy:Gene1atype with compensated cirrhosis after drug discontinuation in patients with different baseline laboratory test values12weeks and24week relapse rate
This product+dasebuvir sodium+ribavirin
12Weekly Treatment GroupThis product+dasebuvir sodium +Ribavirin
24Weekly Treatment GroupNumber of patients who responded at the end of treatment135113Before treatment,AFP* < 20 ng/mL, platelets ≥ 90 x 109/Lalbumin ≥ 35 g/L
Yes (all three parameters above)1/87(1%)0/68 (0%)
No
(any of the above parameters)10/48(21%)1/45 (2%) *AFP= SerumαAFPMeeting three baseline laboratory indices (AFP< 20 ng/mL, platelets≥ 90 x 109/L, albumin≥ 35 g/L) in patients receiving 12weeks orweeks or24weeks of treatment had similar recurrence rates.
TURQUOISE-III: primary orpegIFN+RBVtreated with compensated cirrhosis
Trial design: global multicenter, open study
Treatment regimen: this product+dasebuvir sodium (not combined with ribavirin) treatment12weeks
60 patients were randomized and medicated,60/60(100%) = “font-family:isoline”>) patients obtainedSVR12. The main characteristics of the patient are shown below.
Table13. TURQUOISE-IIIKey demographic data from the study
FeaturesN = 60 Age, median (range) age60.5(26 ~ 78)Male,n(%)37(61)previouslyHCVTreatment history: Hatsumasa27(45)45)Peg-IFN + RBVTreatment,n(%)33(55)baseline albumin, median value (g/L)40.0< 35,n(%)10(17)≥35,n(%)50(83)baseline platelet count, median value (×109/L)132.0< 90,,n(% “font-family:equals”>)13(22)22)22) “padding-left: 7px; padding-right: 7px; border-top: none; border-left: solid 0.5pt; border-bottom: solid 0.5pt; border-right: solid 0.5pt”>≥ 90,n(%)47(78)
Summary analysis of clinical trials
Response Persistence
Overall,2period and 3cases in clinical trials,660 patients were tested forHCV RNAfor the evaluation ofSVR12andSVR24. In these patients,SVR12 onSVR24 had a positive prediction rate of 99.8%.
Summary analysis of validity
In phase 3 clinical trials, the family:Times New Roman”>1075 cases ofHCVgene1type patients (including181 patients with compensated cirrhosis) were treated with the recommended regimen (see [Dosage]). Table14 lists the SVR of these patients. Roman”>SVR rates for these patients.
of patients treated with the recommended regimen, of whom 97%patients obtainedSVR(In 181 cases of compensated cirrhosis,SVRrate was 97%) and only “font-family:Times New Roman”>0.5% of patients had virological breakthroughs, and 1.2%patients experienced relapse after drug discontinuation.
Table14. Different patient populations receiving the recommended regimen of SVR12SVR12rate
HCV Gene1b Type
This product+Dasebuvir sodiumHCVgene1atype
This product+Dasebuvir sodium+Dasebuvir sodium span>ribavirin No cirrhosisCompensated cirrhosisNo cirrhosisCompensated cirrhosisCourse of treatment12weeks12week 12weeks24weeksPrimary patients100%(210/210)100%(27/27)96%(403/420)95% (53/56)pegIFN + RBVTreated patients100%(91/91)100%(33/33)96%(166/173)95%(62/65)Recurring patients100%(33/ 33)100%(3/3)94%(47/50)100%(13/13)Some Respondents 100%(26/26)100%(5/5)100%(36/36)100%(10/10)