Daclatasvir

Daclatasvir Brand Name– Daklinza

What is Daclatasvir

Daclatasvir is an NS5A protein inhibitor approved for the treatment of genotype 1 and 3 chronic hepatitis C virus (HCV) infections in adults, including adults who have undergone liver transplantation, have decompensated cirrhosis, or are coinfected with HIV.

Approval was based on the results of 3, open-label, phase 3 trials (ALLY-1, ALLY-2, and ALLY-3). In the ALLY-3 trial, patients received 60 mg of daclatasvir with sofosbuvir 400 mg PO once daily for 12 weeks; HCV RNA values were measured at post-treatment week 24.

The overall percentage of drug recipients to maintain a sustained virologic response (SVR) was 89% (n = 135/152). Of note, patients without cirrhosis (n = 120) had a higher SVR rate than those with cirrhosis (n = 32), 96% vs. 63%.

For those not achieving the 24 week post-treatment SVR, 1 patient (0.7%) was deemed an on-treatment virologic failure and 16 patients (11%) experienced a relapse. In ALLY-2, adults with HCV and HIV coinfection were administered daclatasvir in combination with sofosbuvir for 12 weeks.

At follow-up, SVR12 were maintained in 97% (n = 123/127) of patients infected with genotype 1 HCV and 100% (n = 10/10) of patients infected with genotype 3 HCV. ALLY-1 evaluated the effectiveness of daclatasvir, in combination with sofosbuvir and ribavirin, in treating genotype 1 HCV infections in adults who had cirrhosis or had undergone a liver transplant.

Data from this trial found 82% (n = 37/45) and 95% (n = 39/41) of cirrhotic and post-liver transplant drug recipients, respectively, maintained SVR12. Daclatasvir is administered once daily, but must be given in combination with sofosbuvir; certain patients require a 3-drug regimen of daclatasvir, sofosbuvir, and ribavirin. 

If administered with ribavirin, all precautions associated with ribavirin also apply to the combination regimen.

In addition, cirrhotic patients infected with HCV genotype 1a should undergo testing for NS5A resistance-associated polymorphisms prior to initiating treatment; specifically, polymorphisms at amino acid positions M28, Q30, L31, and Y93. Daclatasvir was FDA-approved in July 2015.

Indications

1. hepatitis C infection
2. hepatitis C virus

Side Effects

1. anemia
2. diarrhea
3. dizziness
4. elevated hepatic enzymes
5. fatigue
6. headache
7. hepatic failure
8. hepatitis B exacerbation
9. hyperbilirubinemia
10. insomnia
11. nausea
12. rash

Monitoring Parameters

• hepatitis B serology
• LFTs
• plasma hepatitis C RNA
• plasma HIV RNA
• pregnancy testing

Contraindications

• anticoagulant therapy
• antimicrobial resistance
• breast-feeding
• diabetes mellitus
• hepatitis B exacerbation
• hepatitis C and HIV coinfection
• hyperglycemia
• hypoglycemia
• male-mediated teratogenicity
• pregnancy
• pregnancy testing
• use with ribavirin

Interactions

• Abacavir; Dolutegravir; Lamivudine
• Acarbose
• Acetohexamide
• Afatinib
• Albiglutide
• Aliskiren
• Aliskiren; Amlodipine
• Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
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• Aliskiren; Valsartan
• Alogliptin
• Alogliptin; Metformin
• Alogliptin; Pioglitazone
• Alpelisib
• Amiodarone
• Amlodipine; Atorvastatin
• Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
• Amlodipine; Valsartan
• Amoxicillin; Clarithromycin; Lansoprazole
• Amoxicillin; Clarithromycin; Omeprazole
• Antidiabetic Agents
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