Dalatawei is a hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor that inhibits viral RNA replication and viral particle assembly by specifically binding to the N-terminal domain of the NS5A protein.

1、 Drug name

1. Common name: Daclatasvir

2. Product Name: DAKLINZA

2、 Indications

1. Used in combination with sofosbuvir, with or without ribavirin, for the treatment of chronic hepatitis C virus (HCV) genotype 1 or 3 infection.

2. Limitations: The sustained virological response rate of genotype 3 patients with liver cirrhosis treated with daratavir combined with sofosbuvir for 12 weeks is reduced.

3、 Specifications and characteristics

60mg * 28 pills/box.

4、 Main components

Active ingredient: daclatasvir.

5、 Usage and dosage

1. Recommended dosage: 60mg, oral, once daily, taken with meals or on an empty stomach.

2. Combined with sofosbuvir (with or without ribavirin), recommended course of treatment: 12 weeks.

3. If sofosbuvir is permanently discontinued, daratavir should also be discontinued.

6、 Dose adjustment

1. When used in combination with potent CYP3A inhibitors such as clarithromycin, itraconazole, ketoconazole, and ritonavir: the dose is reduced to 30mg once daily.

2. When used in combination with moderate CYP3A inducers such as bosentan, dexamethasone, modafenib, and rifampicin: the dose is increased to 90mg once daily.

3. When used in combination with certain HIV protease inhibitors (such as atazanavir/ritonavir, and the regimen containing carbidostat): the dose is reduced to 30mg once daily (except for darunavir/carbidostat).

4. When used in combination with efavirenz, escitalopram, and nevirapine: the dose is increased to 90mg once daily.

7、 Medication precautions

1. Before and after meals: can be taken with or without food. A high-fat and high calorie meal will slightly reduce the blood concentration of daratavir (Cmax decreased by 28%, AUC decreased by 23%), but there is no need to adjust the dosage.

2. Omission: If missed, please consult a doctor or pharmacist. Dosage should not be missed or skipped during treatment.

3. Vomiting: It is recommended to take the medication as prescribed. If vomiting occurs shortly after taking the medication, consult a doctor.

8、 Medication for special populations

1. Pregnancy: Insufficient human data. No teratogenicity was observed in animal experiments (exposure levels were 6-22 times the recommended human dose). When used in combination with ribavirin, this combination regimen is contraindicated during pregnancy.

2. Breastfeeding: It is unclear whether it is secreted through human milk. It is necessary to balance the benefits of breastfeeding with the mother's medication needs.

3. Children: The safety and efficacy in patients under 18 years old have not yet been determined.

4. Elderly people (≥ 65 years old): No need to adjust dosage. 7% of clinical trial participants are aged 65 years or older, and the safety and SVR12 rate are comparable to younger patients.

5. Renal dysfunction: No dosage adjustment is required for any degree of renal dysfunction. Hemodialysis is unlikely to clear daratavir (high protein binding rate).

6. Liver function impairment: Mild (Child Pugh A), moderate (Child Pugh B), and severe (Child Pugh C) do not require dose adjustment.

9、 Adverse reactions

1. Common (≥ 10%):

Combined use with sofosbuvir: headache (14%), fatigue (14%).

Combination therapy with sofosbuvir and ribavirin: headache, anemia, fatigue, nausea.

2. Serious adverse reactions:

Hepatitis B virus reactivation (in patients with concurrent HBV infection).

When used in combination with sofosbuvir and amiodarone, severe symptomatic bradycardia may occur.

Patients with diabetes may experience changes in blood glucose control (including severe hypoglycemia).

10、 Contraindications

Do not use in combination with potent CYP3A inducers, including but not limited to:

1. Anticonvulsant drugs: phenytoin, carbamazepine.

2. Antimicrobial drug: Rifampicin.

3. Herbal product: St. John's wort (Forsythia suspensa).

11、 Drug interactions

1. Dalatavir is a substrate of CYP3A. Strong inducers of CYP3A reduce its blood drug concentration, while strong inhibitors of CYP3A increase its blood drug concentration.

2. Daratavir inhibits P-gp, OATP1B1/1B3, BCRP, and may increase the blood drug concentration of corresponding substrate drugs (such as digoxin, rosuvastatin, dabigatran etexil, etc.).

3. Combination with amiodarone (including sofosbuvir regimen): Not recommended as it can cause severe bradycardia.

4. Combined use with warfarin: requires frequent monitoring of INR.

5. In combination with diabetes drugs: blood glucose needs to be monitored, and the dosage of hypoglycemic drugs may need to be adjusted.

6. Medications that do not require adjustment of the dose of daratavir: cyclosporine, darunavir/ritonavir, dotravir, escitalopram, ethinylestradiol/norgestrel, lopinavir/ritonavir, methadone, midazolam, tacrolimus, tenofovir, famotidine, omeprazole, sofosbuvir, moderate CYP3A inhibitors (such as azanavir (no enhancer), ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil), etc.

12、 Storage method

1. Storage temperature: 20 ° C to 25 ° C (68 ° F to 77 ° F), allowing short-term fluctuations between 15 ° C to 30 ° C (59 ° F to 86 ° F).

2. Keep at room temperature, in a dry place, away from light. Store out of reach of children.

Daclatasvirinformation