What Are the Different Kinds of Hepatitis C Drugs?

Hepatitis C new drug Peixin injection is mainly used to treat patients without cirrhosis and patients with compensatory stage of cirrhosis.

New drugs for hepatitis C

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Paroxin injection

Pegasys

This product is a sterile vial liquid preparation for subcutaneous injection. In addition to the active ingredients, this product also contains the following excipients: sodium chloride, Tween 80, benzyl alcohol, sodium acetate, acetic acid, water for injection.

The solution was a clear, colorless to pale yellow liquid.

Pegylated interferon -2a is a long-acting interferon formed by the combination of polyethylene glycol (PEG) and recombinant interferon -2a. Interferon binds to specific receptors on the cell surface, triggers complex signaling pathways in cells and rapidly activates gene transcription, and regulates a variety of biological effects, including inhibiting viral replication in infected cells, inhibiting cell proliferation, and having immunomodulatory effects .

After a single subcutaneous injection of PEG interferon -2a 180 ug in healthy people, the activity of serum 2,5-oligoadenylate synthetase (2,5-OAS, an indicator of antiviral activity) increased rapidly 3-6 hours later. The serum activity of 2,5-OAS caused by PEG interferon -2a can be maintained for more than one week, and is higher than that of 3 million units and 18 million units of interferon in a single subcutaneous injection. Compared with young people, a single subcutaneous injection of PEG interferon -2a 180 ug in elderly people over 62 years of age resulted in a decrease in the intensity and duration of serum 2,5-OAS activity.

Pharmacokinetic studies of this product were performed in healthy volunteers and in patients with hepatitis C virus infection.

Absorbed in healthy subject populations, serum concentrations can be detected within 3-6 hours after a single subcutaneous injection of 180 ug. Within 24-48 hours, it can reach 80% of the peak serum concentration. Serum concentration can be maintained for 72-96 hours after injection. Its absolute bioavailability is 84%, which is similar to interferon -2a.

Distribution This product is mainly distributed in blood and extracellular fluid. The volume of steady state distribution after intravenous injection is 6-14 liters. Studies on the material balance, histological distribution, and automatic radioluminescence patterns of this product have been performed in rats. The results show that in addition to high blood concentration, this product is also distributed in the liver, kidney and bone marrow. After this product was radiolabeled, it was not detected in brain tissue after a single intravenous administration.

Metabolism Metabolism is the main mechanism for eliminating this product. The full picture of metabolism is not fully understood. But studies in rats have shown that the kidney is the main organ of excreted radioactive markers and metabolites.

The clearance rate of this product in the human body is about 100 mL / h. 100 times lower than ordinary interferon -2a. After intravenous administration, the half-life is about 60 hours, while ordinary interferon is generally only 3-4 hours. After subcutaneous injection, its half-life is longer (about 80 hours, most patients are between 50-140 hours). The half-life after subcutaneous injection may not reflect the scavenging phase of the compound, but may reflect continuous absorption. The plasma concentration of healthy subjects and patients with chronic hepatitis C once a week increased with the increase of the administered dose. The pharmacokinetic parameters of healthy subjects who received a single subcutaneous injection of 180 ug and chronic hepatitis C patients received a single subcutaneous injection of 180 ug for 48 weeks of treatment once a week.

In patients with chronic hepatitis C, the drug is administered once a week, and after 5-8 weeks in a row, this product accumulates, and its serum concentration can reach 2-3 times that of a single administration. But no further accumulation after 8 weeks. The peak-to-valley ratio after 48 weeks of use is approximately 1.5-2.0. Its serum concentration can maintain a relatively stable level throughout the week.

Patients with abnormal renal function: A study of 23 patients with creatinine clearance above 100 mL / min (normal renal function) to 20 mL / min (significant abnormal renal function) showed that the pharmacokinetics and creatinine clearance of this product There was no significant correlation between rates. In patients with severe renal impairment, the activity of oligoadenylate synthase (OAS) induced by this product is significantly reduced compared with those with normal renal function. However, renal dysfunction has very little effect on the pharmacokinetics of this product.

With a single subcutaneous injection of 90 ug, the tolerability of the product and the incidence of adverse events were similar in subjects with renal dysfunction and healthy subjects, and the frequency of subjects with renal dysfunction only increased slightly. Adverse events and laboratory abnormalities in the study were similar to those seen with ordinary interferon.

Gender: Male and female healthy subjects have comparable pharmacokinetic parameters for a single subcutaneous injection.

Elderly patients: Elderly subjects over 62 years of age have a delayed absorption of this product after giving a single subcutaneous injection of 180 ug compared to healthy subjects, but still persistent. The peak time of the two was 115 hours and 82 hours, respectively; the AUC increased moderately (1663 and 1295 ng / h / mL, respectively); but the peak concentrations were similar (9.1 and 10.3 ng / mL, respectively). Depending on the characteristics of the drug distribution, pharmacodynamic response and drug tolerance, the elderly do not need to adjust the dose.

Patients without and without cirrhosis: The pharmacokinetic characteristics of this product in healthy subjects and in patients with chronic hepatitis C are similar. The drug distribution and pharmacokinetic parameters of patients with compensated cirrhosis and those without cirrhosis are comparable.

Animal experiments suggest that, in connection with other interferons, female monkeys have prolonged menstrual cycles after administration of PEG interferon -2a, accompanied by reduction and delay of 17-estradiol and progesterone peaks. After stopping the drug, menstruation returned to normal; male monkeys were given interferon -2a 25 x 106 IU / kg / day for 5 consecutive months, and no effect on fertility was seen. After the rhesus monkey was given interferon -2a, the abortion rate was significantly increased, and no teratogenesis was found.

Indication

For the treatment of the following chronic hepatitis C patients: patients without cirrhosis and patients with compensatory cirrhosis.

Dosage

The conventional recommended dose is 180 ug, which is administered subcutaneously once a week for a total of 48 weeks.

Special dosage guidelines

General dose adjustment rules: For patients with moderate and severe adverse reactions (including clinical manifestations and / or laboratory abnormalities), the dose should be adjusted. The initial dose is generally reduced to 135 ug, but in some cases the dose needs to be reduced to 90 ug or 45. ug. With the reduction of adverse reactions, you can consider gradually increasing or returning to the conventional dosage.

: When the neutrophil count (ANC) is less than 750 cells / mm3, the reduction should be considered; when the neutrophil count (ANC) is less than 500 cells / mm3, the drug should be temporarily suspended until the ANC returns to more than 1000 cells / mm3 , Can resume treatment. Reinitiation of treatment should use 90 ug and neutrophil count should be monitored.

When the platelet count is less than 50,000 cells / mm3, the dose should be reduced to 90 ug; when the platelet count is less than 25,000 cells / mm3, drug withdrawal should be considered.

Liver function: In patients with chronic hepatitis C, liver function often fluctuates. As with other alpha interferons, ALT elevations also occur after treatment with this product, including patients with a viral response. When a persistent increase in ALT occurs, consideration should be given to reducing the dose to 90 ug. After the reduction, if the ALT continues to increase, or if bilirubin increases or liver function decompensation occurs, drug withdrawal should be considered.

Renal dysfunction in special populations: Patients with renal dysfunction do not need to adjust the dose. Related studies have not been performed in hemodialysis patients.

Hepatic dysfunction: Based on pharmacokinetics, clinical tolerability and safety data, no dose adjustment is needed for patients with liver cirrhosis classified as Child A.

Studies have not been performed in patients with decompensated liver function.

Most of the adverse reactions were mild or moderate, and treatment was not affected. Headache and muscle pain are reported in most patients. The most common (10% of patients) adverse reactions include injection site pain / inflammation, fatigue, chills, fever, depression, joint pain, nausea, hair loss, skeletal muscle pain, irritability, flu-like symptoms, insomnia, diarrhea , Abdominal pain, weakness, pharyngitis, weight loss, anorexia, anxiety, attention disorder, dizziness, and injection site reactions. Common (2% of patients) adverse reactions are itching, dry skin, discomfort, increased sweating, pain in the upper right quadrant of the body, neutropenia, leukopenia, anemia, rash, vomiting, dry mouth, and emotional instability , Nervousness, dyspnea, viral infections, lethargy, thyroid dysfunction, chest pain, indigestion, flushing, paresthesia, cough, irritability, paranasal sinusitis, hypertonia, hypersensitivity, blurred vision, disturbance of consciousness, Flatulence, decreased libido, skin erythema, eye pain, indifferent emotions, decreased sensation, thin stools, conjunctivitis, nasal congestion, constipation, dizziness, excessive menstruation, and menstrual disorders. Mental symptoms are uncommon. Life-threatening psychological symptoms rarely occur. These reactions include suicide, attempted suicide, suicidal ideas, and hallucinations. In patients receiving 0.5 g / kg or 1.0 g / kg of this product, the incidence of granulocytopenia (<0.75 × 109 / L) was 4% and 7%, and thrombocytopenia (<70 × 109 / L) occurred. The rates are 1% and 3%, respectively. In combination with this product and ribavirin, in addition to the adverse reactions that occurred with the above alone medication, the following adverse reactions have also been reported: Common adverse reactions (5% -10%): tachycardia, rhinitis, and abnormal taste . Common adverse reactions (2% -5%): hypotension, syncope, hypertension, lacrimal gland disorders, tremor, bleeding gums, glossitis, gastritis, gastric ulcers, hearing loss / loss, tinnitus, palpitations, thirst, aggressive behavior , Fungal infections, prostatitis, otitis media, bronchitis, respiratory problems, nosebleeds, eczema, abnormal hair quality, photosensitivity and lymphadenopathy. Rare adverse reactions include spasms, pancreatitis, hypertriglyceridemia, arrhythmia, diabetes, and peripheral neuropathy. Aplastic anemia rarely occurs in combination with interferon alpha-2b and ribavirin. Other adverse reactions reported This product may show the following adverse reactions when used alone or in combination with ribavirin: Rare side effects associated with -interferon Ophthalmic conditions include retinopathy (including plaque edema), retinal hemorrhage, retina Arterial and venous embolism, cotton-like exudation, visual acuity and loss of visual field, optic neuritis, and optic papillary edema (see Precautions). The following adverse reactions were rarely reported after the listing of this product: myocardial ischemia, myocardial infarction, exacerbation of sarcoidosis or sarcoidosis, erythema multiforme, Sjogren syndrome, toxic epidermal necrosis, and necrosis at the injection site.

Pregnant women who are allergic to pegylated interferon alpha-2b or any one of the interferons or an excipient. The combination of this product and ribavirin cannot be started before a negative pregnancy response result is obtained. Male patients with spouse pregnancy cannot use this combination of ribavirin for autoimmune hepatitis or liver function in patients with a history of autoimmune diseases. Decompensated or severe renal failure patients (creatinine clearance <50ml / min) ^[3]

Psychological and central nervous system: Rarely reported severe central nervous system reactions during the treatment of this product, especially depression, suicidal ideation, attempted suicide and suicide. Other central system adverse reactions such as aggressive behavior, disturbance of consciousness, and other changes in mental state have also been reported in the treatment of interferon. If a patient has a psychiatric or central nervous system problem (including depression), close monitoring is recommended due to the potential severity of these problems. If symptoms persist or worsen, this product should be discontinued. Cardiovascular aspect: As with the application of interferon alpha, for patients with a history of congestive heart failure, myocardial infarction and / or previous or current arrhythmia, treatment with this product requires close monitoring. It is recommended that patients with previous cardiac abnormalities undergo an electrocardiogram before and during treatment. Arrhythmias (mainly supraventricular) are usually effective for conventional treatment, but this product may need to be discontinued. Acute allergies: Acute allergic reactions (such as urticaria, angioedema, bronchospasm, allergies) are rarely reported during interferon alpha-2b treatment. If this reaction occurs during the use of this product, immediately discontinue the drug and start treatment with appropriate drugs. Transient rashes do not need to be discontinued. Liver function: In patients with signs of decompensated liver function (such as prolonged clotting time), discontinue treatment with this product. Renal function: Patients with renal insufficiency should be closely monitored for signs and symptoms of toxicity. This product should not be used in patients with chronic renal failure or creatinine clearance <50ml / min (see Contraindications). Fever: Although fever during interferon use may be associated with common flu-like syndrome, other causes of persistent fever must be ruled out. Dehydration: Because some patients can see hypotension associated with dehydration when using interferon alpha, patients who take medication should maintain sufficient water and rehydration if necessary. Pulmonary changes: Pulmonary infiltration, localized pneumonia, and pneumonia are occasionally seen in patients treated with alpha interferon, including this product, and even life-threatening. Chest X-rays should be performed on patients with fever, cough, dyspnea or other respiratory symptoms. If chest X-rays show lung infiltration or evidence of impaired lung function, they should be closely monitored and discontinued if necessary. Immediate discontinuation and treatment with corticosteroids may seem to eliminate adverse pulmonary reactions. Autoimmune diseases: During the use of various alpha interferons, different autoantibodies have been reported. During the treatment with interferon, the clinical manifestations of autoimmune diseases are more likely to occur in patients who are prone to autoimmune diseases. Ocular changes: There have been occasional reports of ophthalmic abnormalities after treatment with alpha-interferon, including retinal hemorrhage, cotton-like exudation spots, and retinal artery or vein occlusion (see Adverse Reactions). All patients should undergo basic eye examinations. A timely and comprehensive eye examination must be performed on patients who complain of vision loss or visual field loss. Because these eye abnormalities can also occur in other diseases at the same time, it is recommended that regular visual inspections be performed on patients with diabetes or hypertension. It is recommended to discontinue this product if the patient develops new eye abnormalities or exacerbates existing symptoms during treatment. Thyroid changes: Patients with chronic hepatitis C treated with interferon-alpha rarely have thyroid abnormalities, that is, hypothyroidism or hyperthyroidism. During treatment, if the patient develops symptoms of thyroid dysfunction, a thyroid stimulating hormone (TSH) level is measured. For patients with thyroid dysfunction, this product can only be continued if the thyroid stimulating hormone (TSH) is kept within the normal range through treatment. Metabolic Disorders: Hypertriglyceridemia and severe hypertriglyceridemia have been reported. It is therefore recommended to monitor blood lipid levels. Other aspects: It has been reported that interferon alpha can aggravate preexisting psoriasis and sarcoidosis, so it is recommended that patients with psoriasis and sarcomatosis be considered to use this product only when the benefits outweigh the potential risks. Laboratory examination: All patients who used this product checked blood routine, blood chemistry and thyroid function before treatment. The following baseline indicators can be used as indicators of clinical medication initiation: platelets 100,000 / mm3 neutrophil counts 1,500 / mm3 thyroid stimulating hormone (TSH) levels must be within the normal range, generally during the second week and the second week of the treatment period Laboratory tests were performed for 4 weeks, followed by regular monitoring according to clinical needs. Impact on driving and mechanical operation capabilities: Patients who experience fatigue, drowsiness, or disturbance of consciousness during the treatment of this product should be advised to avoid driving or operating machines.

Medication for pregnant and lactating women

Medication alone

Studies on primates have shown that interferon alpha-2b is an abortion drug. This product may also have this effect. As there is no information on the use of this product in pregnant women, it is not recommended to use this product during pregnancy. It is recommended that women of childbearing age should take effective contraception during treatment with this product. It is unclear whether the ingredients in the drug can be secreted via milk. Therefore, the importance of drugs to lactating women should be considered to decide whether to stop or stop breastfeeding.

Combination medication

This product and ribavirin cannot be used during pregnancy. In spite of the human recommended dose of 1/20, sufficient studies have demonstrated that ribavirin has significant potential for teratogenic and / or embryotoxicity in all animal species. Malformations have been found in the head, upper jaw, eyes, lower jaw, bones and gastrointestinal tract. The incidence and severity of malformations increased with increasing dose of ribavirin. Fetal and offspring survival rates decline. Female patients: pregnant women cannot take ribavirin capsules. Female patients should pay special attention to avoid pregnancy. The combination of this product and ribavirin cannot be started until a negative pregnancy response is obtained. Women of childbearing age and their spouses must take effective contraception during the treatment period and the follow-up period for the next 6 months; during this period, pregnancy tests should be performed monthly. If the patient becomes pregnant during treatment and during the follow-up period of 6 months, the patient must be warned that ribavirin has teratogenic effects on the fetus. Male patients and their spouses: Male patients should avoid pregnancy of their spouses while taking ribavirin. Ribavirin accumulates in cells and clears slowly. In animal studies, ribavirin can alter sperm at subclinical doses. It is unclear whether the sperm containing ribavirin caused teratogenic effects on fertilized eggs. Male patients and their spouses of childbearing age must take effective contraception during treatment and during the follow-up period of 6 months. It is recommended that women of childbearing age can use this product in combination with ribavirin when taking effective contraception during treatment. Lactation: It is unclear whether the ingredients in this drug can be secreted by milk. Due to potential adverse reactions to parenting, it is recommended to stop breastfeeding before treatment begins. ^[1]

The first is blood transfusion and the spread of blood products. Blood transmission was previously the most important transmission route for hepatitis C. However, with the screening of fresh blood in the late 1990s, this transmission method has been significantly controlled. However, due to the current testing methods, blood transfusion can still transmit hepatitis C, especially Repeated blood transfusions and blood products. ^[2]

1. Hepatitis C and Hepatitis B are transmitted in a similar way . Both are transmitted through the blood and are highly contagious.

2. As with hepatitis B, hepatitis C has asymptomatic carriers, but asymptomatic carriers of hepatitis C need antiviral treatment.

3. The clinical manifestations of Hepatitis C are similar to those of Hepatitis B , but there are more asymptomatic and jaundice-free cases of Hepatitis C , so its concealment is better than that of Hepatitis B.

4. Like Hepatitis B , Hepatitis C also tends to develop toward chronic hepatitis and cirrhosis. The difference is that the incidence of chronicization of Hepatitis C is higher than that of Hepatitis B, and it may also develop directly into primary liver cancer.

5. Hepatitis C and Hepatitis B transmission is similar. Cross-infection and overlapping infections can occur, which exacerbates the degree of liver damage and has a higher mortality rate. ^[5]