Daclatasvir: Difference between revisions
→Mechanism of Action: fix ref |
→Research: add ref |
||
| Line 87: | Line 87: | ||
==Research== |
==Research== |
||
Daclatasvir has been tested in combination regimens with [[pegylated interferon]] and [[ribavirin]], as well as with other direct-acting antiviral agents including [[asunaprevir]] and [[sofosbuvir]].<ref>{{cite journal|last1=Sulkowski|first1=Mark S. et al. |title=Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection|journal=New England Journal of Medicine|date=16 January 2014|volume=370|issue=3|pages=211–221|doi=10.1056/NEJMoa1306218|pmid=24428467}}</ref> |
Daclatasvir has been tested in combination regimens with [[pegylated interferon]] and [[ribavirin]],<ref>{{cite journal|last1=Peng|first1=Qin|last2=Li|first2=Kang|last3=Cao|first3=Ming Rong|last4=Bie|first4=Cai Qun|last5=Tang|first5=Hui Jun|last6=Tang|first6=Shao Hui|title=Daclatasvir combined with peginterferon-α and ribavirin for the treatment of chronic hepatitis C: a meta-analysis|journal=SpringerPlus|date=15 September 2016|volume=5|issue=1|doi=10.1186/s40064-016-3218-x|pmid=27652142|pmc=5023653}}</ref> as well as with other direct-acting antiviral agents including [[asunaprevir]] and [[sofosbuvir]].<ref>{{cite journal|last1=Sulkowski|first1=Mark S. et al. |title=Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection|journal=New England Journal of Medicine|date=16 January 2014|volume=370|issue=3|pages=211–221|doi=10.1056/NEJMoa1306218|pmid=24428467}}</ref> |
||
==References== |
==References== |
||
Revision as of 04:42, 9 November 2016
 | |
| Clinical data | |
|---|---|
| Pronunciation | (dak lat' as vir) |
| Trade names | Daklinza |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a615044 |
| Routes of administration | Oral, tablet |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 67% [1] |
| Protein binding | 99% [1] |
| Metabolism | CYP3A |
| Elimination half-life | 12-15 hours |
| Excretion | Fecal (53% as unchanged drug), Renal |
| Identifiers | |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C40H50N8O6 |
| Molar mass | 738.89 g/mol g·mol−1 |
Daclatasvir (trade name Daklinza) is a drug for the treatment of hepatitis C (HCV).
Daclatasvir inhibits the HCV nonstructural protein NS5A.[2] Recent research suggests that it targets two steps of the viral replication process, enabling rapid decline of HCV RNA.
Medical use
Daclatasvir is used only in combination therapy for the treatment of hepatitis C genotype 1 and 3 infections.[1]
Based on animal models, daclatasvir is not shown to cause adverse events at levels used in humans; however, combination therapy with ribavirin is contraindicated in pregnant women and male partners of pregnant women.[1] It is not known whether daclatasvir passes into breastmilk or has any effect on infants.[1] Breastfeeding is safe and does not transmit HCV, however, the CDC recommends avoiding breastfeeding if the infected mother's nipples are cracked or bleeding.[3]
Drug Interactions and contraindications
Concomitant use of drugs that are strong inducers of the cytochrome P450 CYP3A is contraindicated due to decreased therapeutic effect and resistance of drug.[1] Some common drugs that are strong CYP3A inducers include dexamethasone, phenytoin, carbamazepine, rifampin and St. John's Wort.[1]
Daclatasvir is a CYP3A and p-glycoprotein substrate, therefore, drugs that are strong inducers or inhibitors of these enzyme will interfere with daclatascir levels in the body.[1] Dose modifications are made with concomitant use of daclatasvir and drugs that affect CYP3A or p-gp. When taking daclatasvir with non-nucleoside reverse transcriptase inhibitors, the dose of daclatasvir is increased due to CYP3A induction. The dose for daclatasvir should be lowered when taking with antifungals, such as ketoconazole. Currently, there are no required dosage adjustments with concurrent use of daclatasvir and immunosuppressants, narcotic analgesics, antidepressants, sedatives, and cardiovascular agents. [4]
Concurrent use with amiodarone, sofosbuvir and daclatasvir has may result in an increased risk for serious slowing of the heart rate.[1]
Adverse Events
Because it has never been used or studied as monotherapy, it is unknown what specific side effects are linked to this medication alone. Adverse Events on daclatasvir have only been reported on combination therapy with sofusbivir or triple therapy with sofusbivir/ribavirin.[5] Common adverse events, occurring in >10% of patients, on combination therapy (sofusbivir + daclatasvir) include headache and fatigue. In triple therapy use (daclatasvir + sofusbivir + ribavirin), most common adverse events (>10%) include headache, fatigue, nausea and hemolytic anemia.[1]
Pharmacology
Mechanism of Action
Daclatasvir stops HCV viral RNA replication and protein translation by directly inhibiting HCV nonstructural protein 5A or NS5A.[citation needed] It does this by binding directly to NS5A's N-terminus, changing the proteins structure, and thus rendering the protein non-functional.[6] NS5A is critical for HCV viral transcription and translation.[7]
Pharmacokinetics
Daclatasvir reaches steady state in human subjects after about 4 days of once-daily 60 mg oral administration, with a peak dose in concentration occurring about 2 hours after administration.[1] Daclatasvir comes in the form of an oral tablet, with a bioavailability of 67%.[1] Daclatasvir is predominantly metabolized by the liver enzyme CYP3A4, and is also a P-gp substrate.[1] Daclatasvir is highly protein bound. Protein binding was measured to be around 99% in people dosed multiple times with daclatasvir independent of dose strength.[1] Daclatasvir has a volume of distribution of 47L following an oral dose of 60mg and an IV dose of 100ug.[1]
History
Daklinza was developed by Bristol-Myers Squibb.[citation needed]
It was approved for use in Europe in August 2014, in the US in July 2015, and in India in December 2015; different combinations are regimens are used for different HCV genotypes.[8]
Society and culture
It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.[9]
There has been controversy over the price that Bristol-Myers Squibb has chosen to charge for the drug. As of December 2015 it costs between $50,000 and $84,000 in high-income countries.[10]
Research
Daclatasvir has been tested in combination regimens with pegylated interferon and ribavirin,[11] as well as with other direct-acting antiviral agents including asunaprevir and sofosbuvir.[12]
References
- ^ a b c d e f g h i j k l m n o "Daclatasvir label" (PDF). FDA. April 2016.
- ^ Bell, Thomas W. (2010). "Drugs for hepatitis C: unlocking a new mechanism of action". ChemMedChem. 5 (10): 1663–1665. doi:10.1002/cmdc.201000334. PMID 20821796.
- ^ "Sexually Transmitted Diseases Treatment Guidelines, 2015". www.cdc.gov. Retrieved 2016-11-09.
- ^ Garimella, Tushar; You, Xiaoli; Wang, Reena; Huang, Shu-Pang; Kandoussi, Hamza; Bifano, Marc; Bertz, Richard; Eley, Timothy (2016-11-01). "A Review of Daclatasvir Drug-Drug Interactions". Advances in Therapy. 33 (11): 1867–1884. doi:10.1007/s12325-016-0407-5. ISSN 1865-8652. PMID 27664109.
- ^ Institute for Quality and Efficiency in Health Care (February 19, 2015). "Daclatasvir (Daklinza) for hepatitis C: Overview". PubMed Health.
- ^ Modeling shows that the NS5A inhibitor daclatasvir has two modes of action and yields a shorter estimate of the hepatitis C virus half-life. Guedj, J et al. Proceedings of the National Academy of Sciences. February 19, 2013.
- ^ Gao, Min; et al. (2010). "Chemical genetics strategy identifies an HCV NS5A inhibitor with a potent clinical effect". Nature. 465 (7294): 96–100. doi:10.1038/nature08960. PMID 20410884.
{{cite journal}}: Explicit use of et al. in:|author=(help) - ^ "Hepatitis C Treatment Snapshots: Daclatasvir" (PDF). amFAR TreatAsia. February 2016.
- ^ "19th WHO Model List of Essential Medicines" (PDF). WHO. April 2015.
- ^ "Rapid reductions in prices for generic sofosbuvir and daclatasvir to treat hepatitis C." J Virus Erad. 2 (1): 28–31. January 1, 2016. PMC 4946692. PMID 27482432.
- ^ Peng, Qin; Li, Kang; Cao, Ming Rong; Bie, Cai Qun; Tang, Hui Jun; Tang, Shao Hui (15 September 2016). "Daclatasvir combined with peginterferon-α and ribavirin for the treatment of chronic hepatitis C: a meta-analysis". SpringerPlus. 5 (1). doi:10.1186/s40064-016-3218-x. PMC 5023653. PMID 27652142.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Sulkowski, Mark S.; et al. (16 January 2014). "Daclatasvir plus Sofosbuvir for Previously Treated or Untreated Chronic HCV Infection". New England Journal of Medicine. 370 (3): 211–221. doi:10.1056/NEJMoa1306218. PMID 24428467.
{{cite journal}}: Explicit use of et al. in:|first1=(help)
 | This antiinfective drug article is a stub. You can help Wikipedia by expanding it. |