Epclusa drug 400mg/100mg gilead treatment for chronic hepatitis C (28 tablets)
Dosage form Box of 28 tablets
Specifications Sofosbuvir, velpatasvir
Ingredient
| Composition information | Content |
| Sofosbuvir | 400mg |
| Velpatasvir | 100mg |
Uses
indications
Epclusa drugs are indicated in the following cases:
ATC code: Jo5AP55.
Mechanism of action
Sofosbuvir is an inhibitor of all genotypes of RNA polymerase dependent NSSB of HCV, an essential enzyme to copy the virus. Sofosbuvir is a nucleotide fee, undergoing intracellular metabolism to form triphosphate Uridine derivatives with pharmacological activity (GS-461203), which can be combined into the RNA of HCV with NS5B Polymerase and act as a string disconnect component.
GS-461203 (Sofosbuvir's active metabolites) are not inhibitors of DNA and RNA polymerase in humans or RNA polymerase inhibitors in mitochondria.
Velpatasvir is a HCV inhibitor with the target of the NS5A protein of HCV, a protein needed to copy RNA and create HCV virus particles. The studies selected in vitro and cross -drug resistance show that the mechanism of action of Velpatasvir is the effect on the target NS5A.
Viral anti -virus activity
Please see more information about drugs in the instructions for the use of drugs attached.
drug resistance
In cell culture
Symptomatic claims copying units with Sofosbuvir have been selected in cell culture for multiple genotypes, including 1B, 2A, 2B, 3A, 4A, 5A and 6A. The reduction of sensitivity to Sofosbuvir is associated with mutations instead of NS5B is the S282T in all genotypes of copying units that are checked. Creating S282T replacement spot mutations in genotype copying units from 1 to 6 reduces sensitivity to Sofosbuvir from 2 to 18 times and reduces the ability to copy viruses from 89% to 99% compared to the corresponding wild strain. In biochemical trials, the possibility of triphosphate metabolites has the activity of Sofosbuvir (GS-461203) inhibiting the NS5B polymerase re-combination from the genotypes of 1B, 2A, 3A and 4A that the S282T replacement mutation manifests itself reduced compared to the ability to inhibit polymerase NS5B re-organized from the wild strain, as expected by the increase from 8.5 to 24% (IC50).
Selective In vitro the HCV copy units with reduced sensitivity to Velpatasvir has been performed in cell culture for multiple genotypes, including 1A, 1B, 2A, 3A, 4A, 5A and 6A. The variants are selected in positions related to NS5A resistance are 24, 28, 30, 31, 32, 58, 92 and 93. Variants related to drug resistance (RAV) are selected in 2 or more genotypes, F28S, L31I/V and Y93H. The point -oriented mutation with NS5A RAV has shown that replacement mutations reduce the sensitivity to Velpatasvir over 100 times, M28G, A92K and Y93H/N/R/W in genotype 1A, A92K in genotype 1B, C92T and Y93H/N in genotypes 2B, Y93H in genotypes 3, and L31V and P32A/L/Q/R in genotypes 6. The odd test is tested for the 2A, 4A or 5A genotypes that reduce the sensitivity of Velpatasvir more than 100 times. Combining these variants often shows a higher level of reduction in velpatasvir than when only the single radio.
In clinical studies
Research in patients without cirrhosis and patients with cirrhosis are still compensated
In a blistering analysis for patients without cirrhosis or cirrhosis, the use of EPCLusa for 12 weeks in three phase 3, 12 patients (2 patients with genotypes 1 and 10 patients with genotypes 3) eligible for drug resistance analysis due to virus failure. Another patient infected with genotype 3 genotype 3 at the beginning re -infection of genotype medal in a genotype when the virus failure and is excluded from the virus analysis. No patient infected with HCV genotype 2, 4, 5 or 6 encountered a virus failure.
Of the two patients with genotype failure, one patient with viruses with NS5A RAV Y93N has just appeared and the other patient carries viruses with NS5A RAV L31i/V and Y93H when the virus failure. Both patients carry the virus at the beginning containing NS5A RAV. No observations of nucleoside inhibitors (Ni) NS5B at the time of failure in 2 patients.
Of the 10 patients with genotypic viruses 3, Y93H observed in all 10 patients at the time of failure (6 patients with Y93H appeared after treatment and 4 patients with Y93H at the beginning and after treatment). No observation shows NS5B Ni Rav at the time of failure in 10 patients.
Research in patients with unsatisfactory cirrhosis
In a phase 3 study in patients with unprocessed cirrhosis using Epclusa + RBV for 12 weeks, 3 patients (1 patient infected with genotype 1 and 2 patients infected with genotype 3) are eligible for anti -drug analysis due to viral failures. No patient infected with HCV genotype 2 or 4 encountered a virus failure in the EpClusa + RBV treatment group for 12 weeks.
1 patient infected with genotype 1 genotype 1 failed viruses without RAV NS5A or NS5B at the time of failure.
Among 2 patients infected with genotypes of genotypes 3 failed viruses, a patient with NS5A RAV Y93H appeared at the time of failure. Another patient infected with the virus had Y93H at the beginning and when the virus failed and also appeared a low level (less than 5%) of NS5B Ni Rav N142T and E237G at the time of failure. Pharmacokinetic data in this patient is suitable for not adhering to treatment.
In this study, two patients were treated with Epclusa for 12 or 24 weeks without Ribavirin with NS5B S282T that appeared at a low level (less than 5%) and L159F.
The effect of variants related to medical anti -medication at the beginning for the results of treatment
Please see more information about drugs in the instructions for the use of drugs attached.
Cross resistance
In vitro test data shows that most NS5A RAVs are resistant to Ledipasvir and Daclatasvir are still sensitive to Velpatasvir. Velpatasvir is a full -active drug for S282T replacement mutations related to Sofosbuvir resistance in NS5B chain while all mutations are replaced related to Velpatasvir resistance in NS5A chain completely sensitive to Sofosbir. Both Sofosbuvir and Velpatasvir are fully active against replacement mutations related to resistance to other direct impact anti -virus drugs with other mechanisms, such as NS5B inhibitors without nucleoside structure and Protease NS3 inhibitors. The effectiveness of EPCLusa has not been evaluated in patients who have failed when treated with other regimens containing an NS5A inhibitor.
Clinical efficiency and safety
Efficiency of EPCLusa is evaluated in three phase 3 studies in patients infected with genotype from 1 to 6 with or without compensation cirrhosis, a 3rd stage study in patients infected with genotype from 1 to 6 suffered from compensated cirrhosis and a third -stage study in the medium -infected patient with HCV/HIV infection with genotype from 1 to 6 is summarized in Group 1.
| Epclusa 12 weeks SOF+RBV 24 weeka (n = 206)
Having been treated (n = 71) Unprecedented treatment (n = 201)
Having been treated (n = 69) without cirrhosis Astral - 4 is a random study, an open label in patients infected with genotypes of genotypes 1, 2, 3, 4, 5 or 6 and cirrhosis CPT type B. The patient is randomly divided in a ratio of 1: 1: 1 for treatment with Epclusa for 12 weeks, EPCLusA + RBV for 12 weeks or EPCLusA for 24 weeks. Random selection is divided by HCV genotype (1, 2, 3, 4, 5, 6 and unknown). Demographic characteristics and initial characteristics are balanced between treatment groups. Of the 267 patients treated, the median value of age is 59 years old (about 40 to 73); 70% of patients are male; 90% are white; 6% are black; 42% have a body mass index at the beginning of at least 30 kg/m2. The proportion of patients infected with HCV with genotypes 1, 2, 3, 4 or 6 corresponds to 78%, 4%, 15%, 3%and less than 1%(1 patient). No patient infected with HCV genotype 5 is registered to participate. 76% of patients with Alenes IL28B are not CC (CT or TT); 56% has a minimum of 800,000 IU/ml RNA HCV concentration; 55% have been treated; 90% and 95% of patients with cirrhosis CPT type B and end -stage liver disease model (MELD) ≤ 15 at the beginning. Table 6 Presentation SVR12 for Astral-4 study by HCV genotype. genotype 3 No patient infected with HCV genotype 2, 4 or 6 encountered a virus failure. 34.5% (79/229) The frequency of brain disease at the beginning is as follows: 38 % is not available, 62 % degrees 1–2. Clinical studies in co-infection patients with HCV/HIV-1-Astral-5 (Research 1202) Astral-5 has rated 12 weeks of Epclusa treatment in patients infected with genotypes of genotypes 1, 2, 3 or 4 with HIV-1 co-infected (Genotite Geneta 5 or 6 are allowed but no patients this group participates in the research). Patients with Retrovirus HIV-1 anti-resistant treatment are stable using Emtricitabine/Tenofovir Disoproxil Fumarate or abacavir/lamivudine in combination with protease inhibitors to enhance Ritonavir (Atazanavir, Darunavir or Lopinavir), Rilpivirine, Raltegravir or EMRICITABINE/ Tenofovir Disoproxil Fumarate/ Elvitegravir/ CoBicistat. Of the 106 patients treated, the average age is 57 years old (from 25 to 72 years old); 86% of patients are male; 51% is white skin; 45% are black; 22% have initial body mass index ≥ 30 kg/m2; 19 patients (18%) have compensated cirrhosis; and 29% of patients have been treated. The total CD4+ average is 598 cells/UL (about 183–1513 cells/UL). Table 9 Presentation SVR12 for Astral-5 study by HCV genotype. failure during treatment SVR12 achieved in 19/19 patients with cirrhosis. No patient has HIV-1 recurrence during the study period, and the number of CD4+ stable during treatment. Pediatric patients The European medical product management agency has postponed the obligation to submit research results with Epclusa in one or more subgroups of the pediatric population in the treatment of chronic hepatitis C (see section 4.2 for information used for pediatric patients). Elderly Clinical studies with EPCLusa include 156 patients aged 65 and over (12% of the total number of patients in clinical studies phase 3). The observable response rate for patients aged 65 and over is similar to the response rate for patients under 65 years of treatment groups. absorption Sofosbuvir, GS-331007 and Velpatasvir has been evaluated in healthy adults and patients with chronic hepatitis C. After taking oral Epclusa, Sofosbuvir was quickly absorbed and observed that the central concentration in plasma reached 1 hour after taking the drug. It was observed that the central concentration in the plasma of GS-331007 reached 3 hours after taking the drug. It was observed that the central concentration in the velpatasvir plasma at 3 hours after taking the drug. Based on the pharmacokinetic analysis of a complex of HCV infected patients, AUC0-24 average in the stable state of Sofosbuvir (N = 982), GS-331007 (N = 1,428) and Velpatasvir (N = 1,425) are 1,260, 13,970 and 2,970 ng • H/mL. CMAX is in a stable state of Sofosbuvir, GS-331007 and Velpatasvir, respectively 566, 868 and 259 ng/mL. AUC0-24 and CMAX of Sofosbuvir and GS-331007 are similar in healthy adults and HCV infected patients. Compared to healthy subjects (N = 331), AUC0-24 and CMAX of Velpatasvir, which are 37% and 41% of the HCV infected patients. The effect of food Compared to hunger, the use of a single dose of EPCLusa along with a meal with average fat (~ 600 kcal, 30% fat) or high fat (~ 800 kcal, 50% fat) leads to an increase of 34% and 21% AUC0-inF of Velpatasvir and the corresponding increase is 31% and 5% CMAX of VELPATASVIR. Meals have medium or high fat, increasing the AUC0-inf of Sofosbuvir is 60% and 78%, but does not significantly affect Sofosbuvir's CMAX. Meals have medium or high fats that do not change the AUC0-inF of GS-331007 but lead to a reduction of 25% and 37% respectively for CMAX. The response ratio in phase 3 studies is similar in patients infected with HCV using Epclusa with or without food. Can use Epclusa attached or without food. distribution Sofosbuvir binds about 61-65% for human plasma proteins and this link does not depend on the drug concentration of about 1 µg/ml to 20 µg/ml. The protein bond of GS-331007 is at a minimum of the human plasma. After a single dose of 400 mg [14C] Sofosbuvir in healthy objects, the ratio of blood radiation activity on plasma radioactive activity [14C] is about 0.7. Velpatasvir is linked> 99.5% for human plasma proteins and this link does not depend on the drug concentration of 0.09 µg/ml to 1.8 µg/ml. After a single dose of 100 mg [14C] -Velpatasvir in healthy objects, the ratio of radioactive activity in the blood on plasma radioactive activity [14C] fluctuates between 0.52 to 0.67. Biological Change Sofosbuvir is strongly metabolized in the liver to form a triphosphate nucleoside derivative with pharmacological activity GS-461203. The metabolic activation path is related to the carboxyl ester hydrolysis process, catalyzed by Cathepsin A (CATA) or carboxy acidase 1 (CES1) in humans and separating phosphoramidate by protein 1 nucleotide bonds with three amino acids Histidine (Histidine triad nucleotide-binding protein 1 1 Hint1) Chemistry through pyrimidine nucleotide biosynthesis. The process of Dephosphorylation leads to the formation of nucleoside metabolites GS-331007, this substance cannot be effectively re-phosphorylation and inactive in vitro. Sofosbuvir and GS-331007 are not substrates or inhibitors of UGT1A1 or CYP3A4, CYP1A2, CYP2B6, CYP2B6, CYP2C8, CYP2C9, CYP2C9, CYP2C9, CYP2C9, CYP2C9, CYP2, CYP2, CYP2, CYP2, CYP2, CYP2, CYP2, CYP2, CYP2C After using a single dose of 400 mg [14C] -SOFOSBUVIR by oral, GS-331007 accounts for about> 90% in the body exposure. Velpatasvir is the substrate of CYP2B6, CYP2C8 and CYP3A4 with slow metabolic speed. After a single dose of 100 mg [14C] -Velpatasvir, the majority (> 98%) The radioactive activity in plasma is the mother medicine. Velpatasvir's monohydroxylation and desmethylation of Velpatasvir are metabolites determined in human plasma. Velpatasvir is constant is the main component that appears in the feces. Elimination After a single dose of 400 mg [14C] -SOFOSBUVIR through oral, the entire recovery rate of radioactive activity [14C] is over 92%, including about 80%, 14% and 2.5% respectively restored in urine, feces and exhaled air. The majority of Sofosbuvir dose is restored in urine is in the form of GS-331007 (78%) while 3.5% are restored as Sofosbuvir. This data shows that the removal through the kidney is the main elimination sugar of GS-331007. The last semi-waste time of Sofosbuvir and GS-331007 after using Epclusa is 0.5 and 25 hours respectively. After a single dose of 100 mg [14C] -velpatasvir through oral, the entire recovery rate of radioactive activity [14C] is 95%, including about 94% and 0.4%, respectively, recovered in feces and urine. Velpatasvir is constant as the main component in the stool accounting for an average of 77%of the dose, followed by Velpatasvir Monohydroxylation (5.9%) and Velpatasvir Desmethylation (3.0%). This data shows that the excretion of the mother medicine is the main excretion path of Velpatasvir. Velpatasvir's last half -selling time after using Epclusa is about 15 hours. linear/non -linear AUC of Velpatasvir increases almost at the dose ratio on the dose ratio from 25 mg to 150 mg. AUC of Sofosbuvir and GS-331007 increases almost according to the dose ratio on the dose ratio from 200 mg to 1,200 mg. Sofosbuvir/Velpatasvir in Vitro test Sofosbuvir and Velpatasvir are substrates of P-GP and BCRP drug transportation, and GS-331007 is not. Velpatasvir is also the substance of OATP1B. In In vitro testing, Velpatasvir's slow metabolic can be observed via CYP2B6, CYP2C8 and CYP3A4. Velpatasvir is a inhibitor of P-GP, BCRP, OATP1B1 and OATP1B3 and OatP1B3 and the participation of drug interactions with these shipping substances that are mainly limited during absorption. In clinical plasma concentrations, Velpatasvir is not an inhibitor of transportation in the liver of bile salt pump (Bile Salt Export Pump (BSEP), copper protein to transport sodium taurocholate (Sodium Taurocholate Cotransportter Protein -NTCP), OATP2B1, OATP1A2 or Cation Mechanical Transportation (OCT) Transporting in the kidneys 0CT2, 0AT1, 0AT3, Protein 2 related to multi -drug resistance (multidrug resistance -zersociated protein 2 - MRP2) or protein toxins and many drugs (multidrug and toxin extrusion protein - mate) 1, or CYP or enzyme Urridine glucuronosyltransferase (UGT) 1A1. Sofosbuvir and GS-331007 are not inhibitors of P-GP, BCRP, MRP2, BSEP, OATP1B1, OATP1B3, OATP1B3 and 0CT.GS-331007, which are not inhibitors of OAT1, Oct2 and Mate1. pharmacokinetic pharmacokinetics in special patient populations Race and gender It is not determined that the difference in pharmacokinetics is clinically significant due to race or gender for Sofosbuvir, GS-331007 or Velpatasvir. Elderly Popular pharmacokinetics analysis in medals infected with HCV shows that within the age range (18 to 82 years old) analyzed, age without clinical effects on the exposure level of Sofosbuvir, GS-331007 or Velpatasvir. kidney failure Hepatic failure Body weight The body weight has no clinical significance for Sofosbuvir or Velpatasvir exposure according to a population pharmacokinetic analysis. Pediatric patients Not yet established the pharmacokinetics of Sofosbuvir, GS-331007 and Velpatasvir in pediatric patients (see the dose section, how to use). |
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Before taking Epclusa drug 400mg/100mg gilead treatment for chronic hepatitis C (28 tablets)
How to use
Used by oral.
Instruct patients to swallow both tablets with or without food (see pharmacokinetics). Because the drug has a bitter taste, it is recommended not to chew or crush film tablets.
Dosage
The recommended dose of Epclusa is 1 tablet/day, drinking or not with food (see more pharmacokinetics).
Side Effects
When using EPCLusa you may experience unwanted effects (ADR):
Safety records
Safety assessment of Epclusa based on phase 3 clinical research data is synthesized from patients infected with HCV genotype 1, 2, 3, 4, 5 or 6 (with or without compensation cirrhosis) including 1,035 patients using Epclusa for 12 weeks.
The percentage of patients stopped treatment due to harmful reactions was 0.2% and the proportion of patients with serious reactions was 3.2% for patients using EPCLusA for 12 weeks. In clinical studies, headaches, fatigue and nausea are the most common reactions that appear during treatment (the incidence rate ≥ 10%) is reported in patients treated for 12 weeks with Epclusa. These harmful reactions and other harmful reactions are reported with similar frequency in placebo -treated patients compared to patients treated with EPCLusA.
Patients with unsatisfactory cirrhosis
Epclusa's safety profile has been evaluated in an open label study in which patients with CPT CPT cirrhosis use Epclusa for 12 weeks (n = 90), Epclusa + RBV for 12 weeks (n = 87) or Epclusa for 24 weeks (n = 90). Harmful events are consistent with the expected clinical consequences of liver disease, or Ribavirin's known toxicity records for patients using EPCLusa in combination with Ribavirin.
Of the 87 patients treated with EPCLusA + RBV for 12 weeks, the number of cases of haemoglobin reduction is below 10 g/dl and 8.5 g/dl during treatment of 23% and 7% respectively. Stop using Ribavirin in 15% of patients treated with Epclusa + RBV for 12 weeks due to harmful events.
Describe some selective harmful reactions
arrhythmia
Observed cases of serious heart rate slow and heart bloc when using Sofosbuvir in combination with anti -virus drugs that have a direct impact (DAA), used with amiodarone and/or other drugs that slow heart rate (see carefully when used and interact with drugs).
Report cases suspected of harmful reactions
Reporting cases suspected of harmful reactions after licensing of drug circulation is important. This allows continuous monitoring of the balance between the benefits/risks of the drug. Health workers are required to report any case of suspicion of a harmful reaction through the national reporting system.
Instructions on how to handle ADR:
Notify the physician the unwanted effects when taking the drug.
Warnings
Before using the drug you need to read the instructions carefully and refer to the information below.
Contraindicated
Epclusa drug contraindicated in the following cases:
Hypersensitivity to active ingredients or any excipients in the drug.
Use with strong P-GP induction and strong CYP induction:
Medicines are strong Plycoprotein (P-GP) induction (P-GP) or Cytochrome P450 (CYP) strong (Rifampicin, Rifabutin, St. John's Wort [Ban Hypericum Perforatum], Carbamazepine, Phenobarbital VA Phenytoin). Simultaneous use will significantly reduce Sofosbuvir or Velpatasvir plasma concentration and can lead to the effectiveness of Epclusa (see the drug interaction).
Be cautious when using
need to be very careful when taking the drug for patients in the following cases:
Do not use epclusa simultaneously with other drugs containing Sofosbuvir.
Serious heartbeat slow and heart heart
Observed cases of serious heart rate slow and heart bloc when using Sofosbuvir in combination with other direct impact (DAA) anti -drugs, simultaneously used with amiodarone with or without other drugs that slow heart rate. The mechanism has not been identified.
The simultaneous use of Amiodarone is limited to the clinical development program of Sofosbuvir and DAA. These cases can be life -threatening, so only amiodarone should be used for patients being treated with Epclusa when intolerant or contraindicated for other alternative anti -arrhythmic treatments.
When the simultaneous use of Amiodarone is considered necessary, recommending to closely monitor the condition of the patient when starting to use EPCLusA. The patient is determined to have a high risk of slow heart rate that needs to be monitored continuously in 48 hours in appropriate clinical conditions.
Because Amiodarone has a long selling time, it is necessary to follow the appropriate monitoring for patients who have stopped using Amiodarone for a few months and start using EPCLusA.
All patients treated with Epclusa combined with amiodarone have or without other drugs that slow down the heart rate should also be warned of slow heartbeat symptoms and cardiac bloc and recommendations to search for emergency medical support if symptoms appear.
Patients who had previously failed treatment with the regimen containing NS5A
There is no clinical data proving the effectiveness of Sofosbuvir/Velpatasvir in the treatment of patients who have failed with the regimen containing NS5A inhibitors. However, on the basis of variants related to drug resistance (RAV) NS5A commonly found in patients who have been treated failure with other regimens containing NS5A inhibitors, Vitro pharmacology of Velpatasvir and treatment results with Sofosbuvir/Velpatasvir in patients who have never used NS5A NS5A at the beginning time to be registered to participate in Astral research. Use EPCLusA + RBV for 24 weeks for patients who have been treated with failure with NS5A and patients who are said to have a risk of clinical disease progression and patients who have no alternative treatment options.
kidney failure
No need to adjust the dose of Epclusa for patients with mild or medium renal failure. It has not yet been assessed the safety of Epclusa in patients with severe renal failure (EGFR
Use along with the average P-GP induction substance or the average CYP induction substance
P-G-GP or CYP induction drugs average (such as Oxcarbazepine, Modafinil or Efavirenz) can reduce Sofosbuvir or Velpatasvir plasma concentration, which leads to reduced treatment of Epcluseda treatment. It is not recommended to simultaneously use these drugs with Epclusa (see the drug interaction).
Use with some HIV Retrovirus resistance regimens
Epclusa has been shown to increase the ability to expose to Tenofovir, especially when used with HIV treatment regimen containing Tenofovir disoprocil Fumarate and a pharmacokinetic enhancement (ritonavir or cobicistat). The safety of Tenofovir Disoproxil Fumarate Potential risks and benefits are related to simultaneous use of EPCLusA with a fixed combination tablet with doses containing Elvitegravir/Cobicistat/Emtricitabine/Tenofovir disoproxil fumarate or Tenofovir disoproxil Fumarate combined with protease inhibitors HIV enhanced pharmacokinetics (for example Darunavir), especially in patients at risk of kidney dysfunction. The patient is treated with Epclusa in combination with Elvitegravir/CoBicistat/Emtricitabine/Tenofovir Disoproxil Fumarate or Tenofovir Disoproxil Fumarate and HIV Protease Inhibitors are enhanced pharmacokinetics, need to be monitored with harmful reactions related to Tenofovir. Refer to a summary of product characteristics Tenofovir disoproxil fumarate, Emtricitabine/Tenofovir disoproxil fumarate, or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate for recommendations for kidney function monitoring.
co -infection of HCV/HBV (hepatitis B virus)
There have been reports on cases of triggering the hepatitis B virus (HBV), some cases have died, during or after treatment with antiviral drugs directly acting. HBV screening should be conducted for all patients before starting treatment. Because HBV/HCV co -infected patients are at risk of re -trigging HBV, they should be monitored and controlled under the current clinical instructions.
cirrhosis c
Not evaluated the safety and effectiveness of EPCLusa in patients with CPT cirrhosis type C (see the side effects and pharmacological effects).
Patients with liver transplant
Not evaluated the safety and effectiveness of EPCLusa in the treatment of HCV infection in patients after liver transplantation. The treatment with Epclusa at the recommended dose (see the dose, usage) should be adjusted through the assessment of the benefits and potential risks for each patient.
The effect of drugs on driving and operating machinery
Epclusa has no effect or negligible effect on driving and operating machinery.
Use drugs for women during pregnancy and lactation
Pregnant women
No data or very little data (less than 300 cases of pregnancy) use Sofosbuvir, Velpatasvir or Epclusa in pregnant women.
Sofosbuvir
Animal research does not show direct or indirect effects related to reproductive toxicity (see the additional information about drugs in the instruction sheet of using drugs attached).
It is not possible to fully estimate the amplitude of exposure with Sofosbuvir in rats compared to the exposure level in humans at the clinical recommended dose (see information about drugs in the instruction sheet of drug -attached drugs).
velpatasvir
Animal research shows that it may be toxic to fertility (see drug information in the instruction sheet of using drugs attached).
As a preventive measure, recommendations do not use EPCLusA during pregnancy.
Breastfeeding period
It is unclear whether Sofosbuvir, the metabolites of Sofosbuvir or Velpatasvir whether or not the breast milk is excreted.
Animal existing pharmacokinetics in animals shows that the excretion of Velpatasvir and the metabolites of Sofosbuvir through milk.
cannot rule out the risk of infants/young children. Therefore, should not use epclusa while breastfeeding.
fertility
There is no research data in people on the influence of EPCLusa on fertility.
Animal research does not show the harmful effects of Sofosbuvir or Velpatasvir for fertility.
If Ribavirin is simultaneously used with Epclusa, please refer to the drug information in the instructions for the use of the drug attached to know detailed recommendations on pregnancy, contraception and lactation.
Drug interaction
Because Epclusa contains Sofosbuvir and Velpatasvir, any interactions have been determined with each active ingredient can occur with Epclusa.
Epclusa ability affects other drugs
Velpatasvir is a inhibitor of P-GP medication protein, breast anti-cancer protein (organic anion-grathporting polypeptide (BCRP), polypeptide shipping organic anion (organic anion-gedporting polypeptide-OATP) 1B1 and OATP1B3. The simultaneous use of EPCLusa with medications that are substrate for these shipping substances may increase the risk of exposure to those drugs. See Table 3 for examples of interaction with sensitive substrates P-GP (Digoxin), BCRP (Rosuvastatin) and OATP (Pravastatin).
The possibility of other drugs affects Epclusa
Sofosbuvir and Velpatasvir are the substrate of P-GP and BCRP drug transportation. Velpatasvir is also the substrate of polypeptides transporting OATP1B drugs. In In Vitro test, Velpatasvir's slow metabolism was observed by CYP2B6, CYP2C8 and CYP3A4. The drugs are strong P-GP induction substances or strong touch agents CYP2B6, CYP2C8 or CYP3A4 (e.g. Rifampicin, Rifabutin, St. John's Wort, Carbamazepine, Phenobarbital and Phenytoin) can reduce the plasma concentration of Sofosbir or VelpatasVIR, which leads to the effective reduction Sofosbuvir/Velpatasvir. Contraindicated use of these drugs with Epclusa (see the control section). The drug is an average P-GP induction substance or an average CYP induction substance (such as Oxcarbazepine, Modafinil or Efavirenz) that can reduce Sofosbuvir plasma or Velpatasvir plasma that leads to reduction in Epclusa treatment effectiveness. It is not recommended to simultaneously use these drugs with Epclusa (see the cautious part when used). The simultaneous use of P-GP or BCRP inhibitors may increase Sofosbuvir or Velpatasvir plasma. Oatp, CYP2B6, CYP2C8 or CYP3A4 inhibitors can inhibit Velpatasvir's plasma concentration.
There is no expected drug interactions with clinical significance with Epclusa with P-GP, BCRP, OATP or CYP450 inhibitors; Epclusa can be used simultaneously with P-GP, BCRP, OATP and CYP inhibitors.
Patients are treated with vitamin K antagonists
Because liver function can change during treatment with EPCLusa, it is recommended to closely monitor the international standardized index value (INR).
Interaction between epclusa and other drugs
Please see more information about drugs in the instructions for the use of drugs attached.
Storage
Leave a cool place, avoid light, temperatures below 30⁰C.
To be out of reach of children, read the instructions carefully before use.
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