Company: Bristol Myers Squibb Pharmaceuticals.
Legal category: Prescription. Hospital only. Sport permitted.
Active ingredient: Daclatasvir 30mg, 60mg.
Description: Green or light green, biconvex, pentagonal, film-coated tablets marked BMS on one side and 213 or 215 on reverse, respectively.
Presentation: 28, price on request.
Indication: Treatment of chronic hepatitis C virus (HCV) infection in combination with other medicines in adults with genotypes 1, 3, 4.
Pharmacology: Daclatasvir is an inhibitor of nonstructural protein 5A (NS5A), a multifunctional protein that is an essential component of the HCV replication complex. Daclatasvir inhibits both viral RNA replication and virion assembly.
Dosage: Adult: Swallow whole. 60mg once daily. Genotype 1/4 without cirrhosis: Daklinza + sofosbuvir, 12 weeks (consider 24 weeks for patients with prior treatment including a NS3/4A protease inhibitor). Genotype 1/4 with compensated cirrhosis: Daklinza + sofosbuvir, 24 weeks (consider 12 weeks for treatment naïve patients with positive prognostic factors such as IL28B CC genotype/low baseline viral load; consider adding ribavirin for patients with very advanced liver disease/other negative prognostic factors such as treatment experience). Genotype 3 with compensated cirrhosis/treatment experienced: Daklinza + sofosbuvir + ribavirin, 24 weeks. Genotype 4: 24 weeks of Daklinza with 24 weeks (if HCV RNA undetectable at weeks 4 and 12) or 48 weeks of peginterferon alfa and ribavirin. Concomitant strong CYP3A4 inhibitors: 30mg Daklinza once daily. Concomitant moderate CYP3A4 inducers: 90mg Daklinza once daily. Elderly: As per adults. Children: Under 18 years, not recommended.
Contraindications: Hypersensitivity to the active substance or to any of the excipients. Pregnancy, lactation. Women should use contraception during and for 5 weeks after treatment (extreme care in female patients and female partners of male patients taking ribavirin; see ribavirin SPC).
Special precautions: Do not use as monotherapy. Inadequate virologic response (discontinue). HCV RNA >1000 IU/ml at week 4 or ≥25 IU/ml at week 12, discontinue Daklinza, peginterferon alfa and ribavirin; HCV RNA ≥25 IU/ml at week 24: (discontinue peginterferon alfa and ribavirin). Safety and efficacy not established: Decompensated liver disease, organ transplant patients, HIV/HBV co-infection. Cirrhosis (limited data in combination with sofosbuvir only). Genotype 1 and compensated cirrhosis, limited experience. Genotypes 2 and 3, limited data. Genotypes 5 and 6, not studied. See SPC of drugs used in combination with Daklinza before initiation. Driving/using machines. Contains lactose.
Drug interactions: Contraindicated: Strong CYP3A4 and P-glycoprotein transporter (P-gp) inducers. Not recommended: Darunavir, lopinavir, etravirine, nevirapine. Caution: Amiodarone (including within past few months), P-gp/ OATP 1B1/ OCT1/ BCRP substrates (especially if narrow therapeutic range), erythromycin, calcium channel blockers. Moderate P-gp inducers (adjust dose), intestinal P-gp substrates with a narrow therapeutic range.
Adverse drug reactions: Fatigue, headache, gastrointestinal disorders. In combination with peginterferon alfa and ribavirin or with sofosbuvir ± ribavirin: Pruritus, insomnia, dry skin, decreased appetite, alopecia, rash, irritability, myalgia, anaemia, cough, dyspnoea, arthralgia. In combination with peginterferon alfa and ribavirin only: Influenza-like illness, pyrexia, neutropenia, lymphopenia. In combination with sofosbuvir ± ribavirin only: Depression, anxiety, dizziness, migraine, hot flush, exertional dyspnoea, nasal congestion.
Full prescribing information and references available from Bristol Myers Squibb Pharmaceuticals. Telephone: 1 800 749 749. E-mail: medical.information@bms.com