Chemical formula: C₄₀H₅₀N₈O₆ Molecular mass: 738.89 g/mol PubChem compound: 25154714
There are no data from the use of daclatasvir in pregnant women. Studies of daclatasvir in animals have shown embryotoxic and teratogenic effects. The potential risk for humans is unknown. Daclatasvir should not be used during pregnancy or in women of childbearing potential not using contraception. Use of highly effective contraception should be continued for 5 weeks after completion of daclatasvir therapy.
Since daclatasvir is used in combination with other agents, the contraindications and warnings for those medicinal products are applicable. For detailed recommendations regarding pregnancy and contraception, refer to the Summary of Product Characteristics for ribavirin and peginterferon alfa.
It is not known whether daclatasvir is excreted in human milk. Available pharmacokinetic and toxicological data in animals have shown excretion of daclatasvir and metabolites in milk. A risk to the newborn/infant cannot be excluded. Mothers should be instructed not to breastfeed if they are taking daclatasvir.
No human data on the effect of daclatasvir on fertility are available. In rats, no effect on mating or fertility was seen.
Dizziness has been reported during treatment with daclatasvir in combination with sofosbuvir, and dizziness, disturbance in attention, blurred vision and reduced visual acuity have been reported during treatment with daclatasvir in combination with peginterferon alfa and ribavirin.
The overall safety profile of daclatasvir is based on data from 2215 patients with chronic HCV infection who received daclatasvir once daily either in combination with sofosbuvir with or without ribavirin (n=679, pooled data) or in combination with peginterferon alfa and ribavirin (n=1536, pooled data) from a total of 14 clinical studies.
The most frequently reported adverse reactions were fatigue, headache, and nausea. Grade 3 adverse reactions were reported in less than 1% of patients, and no patients had a Grade 4 adverse reaction. Four patients discontinued the daclatasvir regimen for adverse events, only one of which was considered related to study therapy.
The most frequently reported adverse reactions were fatigue, headache, pruritus, anaemia, influenza-like illness, nausea, insomnia, neutropenia, asthenia, rash, decreased appetite, dry skin, alopecia, pyrexia, myalgia, irritability, cough, diarrhoea, dyspnoea and arthralgia. The most frequently reported adverse reactions of at least Grade 3 severity (frequency of 1% or greater) were neutropenia, anaemia, lymphopenia and thrombocytopenia. The safety profile of daclatasvir in combination with peginterferon alfa and ribavirin was similar to that seen with peginterferon alfa and ribavirin alone, including among patients with cirrhosis.
Adverse reactions are listed below by regimen, system organ class and frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000) and very rare (<1/10,000). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Adverse reactions in clinical studies:
| System Organ Class | Adverse Reactions | |
|---|---|---|
| Frequency | Daclatasvir + sofosbuvir + ribavirin Ν=203 | Daclatasvir + sofosbuvir N=476 |
| Blood and lymphatic system disorders | ||
| very common | anaemia | |
| Metabolism and nutrition disorders | ||
| common | decreased appetite | |
| Psychiatric disorders | ||
| common | insomnia, irritability | insomnia |
| Nervous system disorders | ||
| very common | headache | headache |
| common | dizziness, migraine | dizziness, migraine |
| Vascular disorders | ||
| common | hot flush | |
| Respiratory, thoracic and mediastinal disorders | ||
| common | dyspnoea, dyspnoea exertional, cough, nasal congestion | |
| Gastrointestinal disorders | ||
| very common | nausea | |
| common | diarrhoea, vomiting, abdominal pain, gastrooesophageal reflux disease, constipation, dry mouth, flatulence | nausea, diarrhoea, abdominal pain |
| Skin and subcutaneous tissue disorders | ||
| common | rash, alopecia, pruritus, dry skin | |
| Musculoskeletal and connective tissue disorders | ||
| common | arthralgia, myalgia | arthralgia, myalgia |
| General disorders and administration site conditions | ||
| very common | fatigue | fatigue |
In clinical studies of daclatasvir in combination with sofosbuvir with or without ribavirin, 2% of patients had Grade 3 haemoglobin decreases; all of these patients received daclatasvir + sofosbuvir + ribavirin. Grade ¾ increases in total bilirubin were observed in 5% of patients (all in patients with HIV co-infection who were receiving concomitant atazanavir, with Child-Pugh A, B, or C cirrhosis, or who were post-liver transplant).
Cases of severe bradycardia and heart block have been observed when daclatasvir is used in combination with sofosbuvir and concomitant amiodarone and/or other drugs that lower heart rate.
The safety and efficacy of daclatasvir in children and adolescents aged <18 years have not yet been established. No data are available.
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