Drug reference, instructions for use, reviews on medicines, medicines, medicines rating, reviews of users and doctors, special instructions, side effects, overdose, application, testimony Sovaldi is an inhibitor OF ns5b polymerase of hepatitis C virus (HCV) and is used for the treatment of chronic hepatitis C (HCV) as a component of the combined regimen of antiviral therapy in adult patients in combination with other medicines. Clinical data on the use of sofosbuvir in patients with genotype 5 or 6 are limited. Data on the efficacy of the drug in patients with co-infection hepatitis and HIV are not as per the hepatitis c treatment guidelines.
Sofosbuvir is a pangenotypic inhibitor of hepatitis C virus NS5B RNA polymerase, which is important for virus replication. Sofosbuvir is nucleotide depo-form, which after participation in the intracellular metabolism generates pharmacologically active originalului triphosphate (GS-461203), which can be entered in the RNA of hepatitis C virus NS5B polymerase and acts as the agent that breaks the chain. In the biochemical analysis of GS-461203 inhibited the polymerase activity recombinantes NS5B from hepatitis C virus genotypes 1b, 2a, 3a and 4a with values of 50% inhibitory concentration (IC 50 ) in the range from 0.7 to 2.6 µm. GS-461203 (active metabolite sofosbuvir) is not an inhibitor of human DNA and RNA polymerase, nor is it an inhibitor of mitochondrial RNA polymerase.
In the analysis of HCV replication the value of effective concentration (EC50 ) sofonovich vs full sizeThe REPLICATION of 1a, 1b, 2a, 3a and 4a genotypes were 0.04, 0.11, 0.05, 0.05 and 0.04 µm respectively, and the EC50 sofosbuvir versus hybrid 1B REPLICATIONS encoding the ns5b genotype 2b, 5a or 6a were 0.014 to 0.015 µm. In these analyses, the antiviral effect of sofosbuvir in vitro against less common genotypes 4, 5 and 6 was similar to that observed in genotypes 1, 2 and 3.
The presence of 40% human serum had no effect on the antiviral activity of sofosbuvir to HCV.
Indications for use:
Stick is used in combination with other drugs for the treatment of chronic hepatitis C (CHC) in adults. Method of application:
The use of sovaldi hep c should begin under the supervision of a doctor with experience in treating patients with CHC..
Patients should be told that if for 2:00 after ingestion there luvanna, you should take another pill. If vomiting occurs more than 2:00 after taking the tablet, take an additional dose is not necessary. These recommendations are based on the absorption kinetics of sofosbuvir and GS-331007, indicating that most of the dose is absorbed within 2:00 after taking it.
Patients should be informed that if they miss the dose and after that it will take 18 hours, the patient should immediately take the missed pill and then take the pill at the usual time. If it has been more than 18 hours should take the next dose at the usual time, without doubling it.
Adverse reactions by organ classes of body organ systems and frequency.
Frequency classification: very often (≥1 / 10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), singly (≥1 / 10000 to < 1/1000) or rarely (<1/10 000). Side reactions associated with the use of sofosbuvir in combination with ribavirin or interferon Alfa-2 and ribavirin Infections and parasitic infestation: often - rhinopharyngitis. Disorders of the circulatory and lymphatic systems: very often - reduced hemoglobin, anemia, neutropenia, decreased lymphocytes, reduced platelet count, often - anemia. On the part of metabolism and nutrition: very often - reduce appetite, often - weight loss. Psychiatric disorders: very often - insomnia, depression, excitement, arousal. Disorders of the nervous system: very often - headache, dizziness, headache, often - impaired attention, migraine, memory impairment, impaired attention, visual impairment, often - blurred vision. From the respiratory system, chest and mediastinal organs: very often - shortness of breath, cough, often-shortness of breath, shortness of breath under physical exertion, cough. From the gastrointestinal tract: very often-nausea, diarrhea, vomiting, often - discomfort in the abdomen, constipation, dyspepsia, constipation, dry mouth, gastrointestinal reflux. From the liver and biliary system: very often - increased bilirubin in the blood. From the skin and subcutaneous tissues: very often - rash, itching, often-baldness, dry skin, itching. From the musculoskeletal and connective tissues: very often - arthralgia, myalgia, often-arthralgia, back pain, muscle spasms, myalgia. Systemic disorders and disorders at the injection site: very often - fatigue, irritability, chills, flu - like diseases, pain, fever, often-fever, General weakness, chest pain. Contraindications: Hypersensitivity to active ingredients or other components of the drug. Caution should be exercised in women of reproductive age. When using Sovaldi as a hepatitis c medication in combination with ribavirin and interferon alpha pregnancy is undesirable. Avoid the use of medications during pregnancy and lactation. There are no data on the effect of the drug on reproduction. Pregnancy: There are no data on the use of Sovaldi in pregnant women or they are limited (less than 300 cases of pregnancy). The study found no direct or indirect harmful effects on animals in relation to reproductive toxicity. In the study, with the use of high doses for rats and rabbits, no effect on embryo development was not detected. However, it is impossible to fully assess the levels of sofosbuvir exposure in rats relative to the effect of the recommended clinical dose on humans. As a preventive measure, it is recommended to avoid the use of Sovaldi during pregnancy. However, if together with sofosbuvir used ribavirin, should comply with contraindications for the use of ribavirin during pregnancy (see also Instructions for the use of ribavirin). It is unknown, sofosbuvir and its metabolites are excreted in human breast milk. The available pharmacokinetic data on animals are indicated for the elimination of metabolites with milk. Risks for newborns / infants cannot be excluded. Thus, Sovaldi should not be used breastfeeding. Data on the impact of Sovaldi on human reproductive function are insufficient. Animal studies do not indicate harmful effects on reproductive function. Interaction with other drugs: Sofosbuvir-depot - a form of nucleotide. After using Sovaldi sofosbuvir is rapidly absorbed and subject to intensive primary metabolism in the liver and stomach. The hydrolytic disintegration of the depot form in the cell, catalyzed including enzymes, carboxylesterases 1 and serial fosfaurilaza catalyzed nucleotide chinnasami to cause the formation of pharmacologically active triphosphate, an analog originallity. The main inactive circulating metabolite GS-331007, which is responsible for more than 90% of the systemic action of the derivative materials of the drug, is formed in sequential and parallel ways to the formation of the active metabolite. Output sofosbuvir is responsible for the systemic action of approximately 4% of the derivative materials (see section "Pharmacokinetics"). In pharmacological clinical trials were monitored for sofosbuvir and GS-331007 with the purpose of pharmacokinetic analysis. Sofosbuvir is a substrate for The p-glycoprotein Transporter drug and the breast cancer resistance protein (BCRP), and GS-331007 is not a substrate. Medicines, which are strong inducers Of p-glycoprotein in the stomach (for example rifampicin, St. John's wort, carbamazepine and phenytoin), can reduce the concentration of sofosbuvir in plasma, which will reduce the therapeutic effect of Sovaldi, and therefore they should not be taken with Sovaldi (see "Special warnings"). Co-administration of Sovaldi with drugs that are inhibitors of P-glycoprotein and / or BCRP can cause an increase in the concentration of sofosbuvir in plasma without increasing the concentration of GS-331007 in plasma, so Sovaldi can be used with p-glycoprotein inhibitors and / or BCRP. Sofosbuvir and GS-331007 are not inhibitors of P-glycoprotein and BCRP, so the effect of drugs that are substrates for these transporters is not expected to increase. The pathway of metabolic activation of sofosbuvir in a cell is mediated by the generally low formation of bonds and effective hydrolysis, as well as by the paths of nucleotide phosphorelation, which are unlikely to be influenced by concomitant drugs. Overdose: Maximum recorded dose of sofosbuvir corresponds to one of neterpenie dose of 1200 mg, which is designed to 59 healthy patients. The study at this dose level was not detected harmful effects and adverse reactions similar in frequency and severity to those reported in the therapeutic groups took a placebo or 400 mg sofosbuvir. The consequences of taking high doses are unknown. In case of overdose Savaldi there's no antidote. In case of overdose, the patient should be examined for toxic effects. Treatment for the overdose of Sovaldi consists in General supportive measures, including monitoring of life indicators, as well as monitoring the clinical condition of the patient. Hemodialysis can effectively withdraw (53% purification rate) the main circulating metabolite GS-331007. 4-hour hemodialysis procedure brought 18% of the dose. Storage conditions: Store at a temperature not exceeding 30 ° C. Keep out of reach of children. Form release: Sovaldi-tablets coated with a film. White bottle made of high density polyethylene (HDPE), closed with aluminum foil with a polypropylene cover to protect children, contains 28 tablets, film-coated with silica gel desiccant and polyester coil. 1 bottle in a carton. Composition: 1 coated tablet, Sovaldi contains 400 mg sofosbuvir. Auxiliary substances: mannitol (E 421), microcrystalline cellulose, sodium croscarmellose, silicon colloidal dioxide, magnesium stearate. Shell tablets: polyvinyl alcohol, titanium dioxide, macrogol, talc. Additionally: Sovaldi is not recommended as monotherapy and should be prescribed in combination with other drugs for the hepatitis C treatment .in case of discontinuation of the use of drugs in combination with Sovaldi, Sovaldi should also be discontinued (see section "dosage and Administration"). Before you start treatment Savoldi, check out the list of medicines that can be administered with this drug. Patients with 1, 4, 5 and 6 HCV genotypes who have already been treated The effect of Sovaldi on patients with 1, 4, 5 and 6 HCV genotypes who were treated was not studied. Care should be taken to treat such patients and, if possible, extend treatment with sofosbuvir, interferon alpha-2 and ribavirin from 12 to 24 weeks. This is particularly the case for subgroups of patients who have one or more factors historically associated with a lower rate of response to interferon-based treatment (expressed fibrosis / cirrhosis, high initial concentrations of the virus, Negroid race, IL28B, except the CC genotype). Patients with 5 or 6 genotypes of HCV infection treated Data on the use of Sovaldi patients with 5 and 6 genotypes of HCV infection, treated very limited (see section "Pharmacological"). Patients 1, 4, 5 and 6 genotypes of HCV infection receiving therapy without interferon Modes bezynertsionnoj the treatment of patients with 1, 4, 5 and 6 genotypes of HCV infection with the use of Cavaldi in the phase 3 studies have not been studied (see Section "Pharmacological"). The optimal regimen and duration of treatment have not been established. Such regimens should only be used for patients with intolerance or who are not eligible for interferon therapy if necessary. Combined use with other direct-action antiviral drugs against HCV Sovaldi should be used in conjunction with other direct-acting antiviral drugs, only if based on available data it is believed that their effectiveness is dominated by risks. There is no data to support the joint use of Sovaldi and telaprevir or boceprevir. Concomitant use not recommended (see also Section "Interaction with other medicinal products and other forms of interaction"). Symptomatic bradycardia in a joint application with amiodarone and other antiviral drugs of direct action against HCV With the joint application of amiodarone and Sovaldi in combination with daclatasvir and simeprevir, post-registration cases of symptomatic bradycardia and cases requiring the use of a pacemaker were recorded in patients. Reported lethal outcome as the result of heart failure from the patient who were administered amiodarone in combination with drugs containing sofosbuvir (harbone (ledipasvir / sofosbuvir)). Usually bradycardia lasted from several hours to several days, but there were also cases when it did not disappear until 2 weeks after the start of HCV treatment. Patients who also take beta-blockers, or patients with significant concomitant heart diseases and / or progressive liver disease are at increased risk of developing symptomatic bradycardia when combined with amiodarone. Bradycardia usually disappears after discontinuation of treatment for HCV. The mechanism of this effect is unknown. Joint application of amiodarone and Sovaldi in combination with other antiviral drugs of direct action against HCV is not recommended. For patients taking amiodarone, who do not have other alternatives to life-saving treatment and who will use Sovaldi in combination with other antiviral drugs of direct action, it is advisable: Consult your doctor about the risk of symptomatic bradycardia. To provide cardiac monitoring in the hospital during the first 48 hours, the joint use of drugs, then you should arrange daily outpatient compulsory monitoring or self-monitoring heart rate at least in the first 2 weeks of treatment. Patients who use Sovaldi as a in combination with other antiviral drugs of direct action and who need to start therapy with amiodarone due to the lack of alternative treatments should also be provided with cardiomonitoring in the above method. Because amiodarone has a long half-life, patients who stopped taking the amiodarone just before the beginning of the application Savaldi in combination with other antiviral drugs direct action, should also provide cardiac monitoring in the above method. Patients who develop signs or symptoms of bradycardia, you should immediately consult a doctor. Symptoms may be of a nature: light-headedness, fainting, dizziness or lightheadedness, anxiety, weakness, excessive fatigue, shortness of breath, chest pains, confusion or memory problems. Application with potential inductors of P-glycoprotein Drugs that are strong inducers Of p-glycoprotein in the intestine (for example, rifampicin , St. John's wort [Hypericum perforatum], carbamazepine and phenytoin) can significantly reduce the concentration of sofosbuvir in plasma, which will reduce the therapeutic effect of Sovaldi. Such drugs should not be used with Sovaldi (see section "Interaction with other drugs and other types of interactions"). Violation of kidney function The safety of Sovaldi in patients with acute renal insufficiency (rscd <30 ml / min / 1.73 m 2 ) or chronic renal insufficiency in need of hemodialysis has not been assessed. A proper dose has also been established. If Sovaldi is used in combination with ribavirin or interferon Alfa-2 / ribavirin, see also ribavirin instruction for patients with creatinine clearance (CrCl) <50 ml / min (see also "Pharmacokinetics"). Co-infection HCV / HBV (hepatitis B virus) There are no data on the use of Sovaldi in patients with HCV / HBV coinfection. Children's population Sovaldi is not recommended for children (under the age of 18), because safety and efficacy has not been established for this population.