Daclatasvir dihydrochloride

Daclatasvir dihydrochloride
INN
Drug class
Routes of administration	Oral
Pregnancy category
Bioavailability
Metabolism	Liver (CYP3A)
Elimination half-life	12–15 hours
Excretion	Feces (88%), urine (6.6%)
Legal status
CAS Number	1009119-64-5
PubChem	25154714
DrugBank	DB09102
ChemSpider	25074884
KEGG	D09931

Daclatasvir dihydrochloride is an antiviral drug used in the treatment of hepatitis C virus (HCV) infection. It is a direct-acting antiviral agent that targets the nonstructural protein 5A (NS5A) of the virus, inhibiting viral replication.

Mechanism of Action

Daclatasvir is a potent inhibitor of the HCV NS5A protein, which is essential for viral replication and assembly. By binding to NS5A, daclatasvir disrupts the formation of the replication complex, thereby inhibiting the synthesis of viral RNA. This action effectively reduces the viral load in patients infected with HCV.

Pharmacokinetics

Daclatasvir is administered orally and has a high bioavailability. It is extensively bound to plasma proteins, with a protein binding rate of approximately 99%. The drug is metabolized primarily by the liver enzyme cytochrome P450 3A (CYP3A). The elimination half-life of daclatasvir is between 12 to 15 hours, and it is excreted mainly in the feces (88%) and to a lesser extent in the urine (6.6%).

Clinical Use

Daclatasvir is used in combination with other antiviral agents, such as sofosbuvir, for the treatment of chronic HCV infection. It is effective against multiple genotypes of the virus, including genotypes 1, 2, 3, and 4. The combination therapy has been shown to achieve high rates of sustained virologic response (SVR), which is considered a cure for HCV infection.

Adverse Effects

Common adverse effects of daclatasvir include headache, fatigue, nausea, and diarrhea. Serious adverse effects are rare but may include bradycardia when used in combination with sofosbuvir and amiodarone. Patients should be monitored for potential drug interactions, especially with drugs that are substrates, inhibitors, or inducers of CYP3A.

Drug Interactions

Daclatasvir is a substrate of CYP3A, and its plasma concentrations can be affected by drugs that modulate this enzyme. Strong CYP3A inducers, such as rifampin and carbamazepine, can significantly reduce the effectiveness of daclatasvir by decreasing its plasma levels. Conversely, strong CYP3A inhibitors, such as ketoconazole, can increase daclatasvir levels and the risk of adverse effects.

Contraindications

Daclatasvir is contraindicated in patients with hypersensitivity to the drug or any of its components. Caution is advised when prescribing daclatasvir to patients with severe hepatic impairment, as the pharmacokinetics of the drug may be altered.

Pregnancy and Lactation

Daclatasvir is classified as a pregnancy category B1 drug in Australia, indicating that there is no evidence of harm to the fetus in animal studies, but human data are lacking. It is not known whether daclatasvir is excreted in human milk, so caution should be exercised when administering the drug to breastfeeding women.

Conclusion

Daclatasvir dihydrochloride is a key component in the treatment of chronic hepatitis C infection, offering a high rate of cure when used in combination with other antiviral agents. Its role in inhibiting the NS5A protein makes it a valuable tool in the fight against HCV, although careful consideration of drug interactions and patient-specific factors is necessary to ensure safe and effective use.

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