出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2020/05/10 04:02:09」(JST)
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| Trade names | Harvoni (combination with sofosbuvir) |
| Other names | GS-5885 |
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| Routes of administration | by mouth |
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| Pharmacokinetic data | |
| Bioavailability | 76% |
| Protein binding | >99% |
| Metabolism | No cytochrome metabolism |
| Elimination half-life | 47 hrs |
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| Formula | C49H54F2N8O6 |
| Molar mass | 889.00 g/mol g·mol−1 |
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Ledipasvir is a drug for the treatment of hepatitis C that was developed by Gilead Sciences.[1] After completing Phase III clinical trials, on February 10, 2014 Gilead filed for U.S. approval of a ledipasvir/sofosbuvir fixed-dose combination tablet for genotype 1 hepatitis C.[2][3] The ledipasvir/sofosbuvir combination is a direct-acting antiviral agent that interferes with HCV replication and can be used to treat patients with genotypes 1a or 1b without PEG-interferon or ribavirin.
Ledipasvir is an inhibitor of NS5A, a hepatitis C virus protein.
Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of the nucleotide analog inhibitor sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.[4][5] The sofosbuvir/ledipasvir coformulation is being tested with and without ribavirin. In February 2014 Gilead filed for United States Food and Drug Administration (FDA) approval of ledipasvir/sofosbuvir oral treatment, without interferon and ribavirin.[6]
On 10 October 2014 the FDA approved the combination product ledipasvir/sofosbuvir called Harvoni.[7]
Ledipasvir is most commonly used in combination with sofosbuvir for treatment in chronic hepatitis C genotype 1 patients. This drug has been tested and shown efficacy in treatment-naive and treatment experienced patients.[8]
According to clinical trials, ledipasvir/sofosbuvir has been very well tolerated with the most common side effects being fatigue and headache.[9]
Most drug-drug interactions with Harvoni involve Pgp-inducers such as St. John’s wort or rifampicin. Concomitant use will decrease the blood concentration of Harvoni and thus, have reduced therapeutic effects.[9]
Ledipasvir inhibits an important viral phosphoprotein, NS5A, which is involved in viral replication, assembly, and secretion.[10]
Sofosbuvir, on the other hand, is metabolized to a uridine triphosphate mimic, which acts as a RNA chain terminator when incorporated into RNA by NS5B polymerase.[10]
Similar to sofosbuvir, the cost of Harvoni has been a controversial topic. It costs $1,125 per pill in the US, translating to $63,000 for an 8-week treatment course, $94,500 for a 12-week treatment course, or $189,000 for a 24-week treatment course. Gilead justifies the cost by outweighing the benefit of curing hepatitis C over the cost of spending double on liver transplants or temporarily treating liver diseases. Gilead has provided a ledipasvir/sofosbuvir assistance program for eligible underserved or underinsured hepatitis C patients who cannot afford the costs of treatment.[10]
In July 2015 Gilead modified the eligibility criteria to receive Support Path benefits for HCV patients in the United States.
RNA virus antivirals (primarily J05, also S01AD and D06BB) | |||||||||
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| リンク元 | 「C型肝炎」「レジパスビル」 |
| 一般名 | 略号 | 販売名 | 作用点 | |
| アスナプレビル | asunaprevir | ASV | スンベプラ | HCV NS3/4Aプロテアーゼ阻害 |
| エルバスビル | elbasvir | EBR | エレルサ | HCV NS5A阻害 |
| グラゾプレビル | grazoprevir | GZR | グラジナ | HCV NS3/4Aプロテアーゼ阻害 |
| グレカプレビル・ピブレンタスビル | glecaprevir/pibrentasvir | GLE/PIB | マヴィレット配合 | HCV NS3/4Aプロテアーゼ阻害・HCV NS5A阻害 |
| ソホスブビル | sofosbuvir | SOF | ソバルディ | 核酸アナログ |
| ソホスブビル・ベルパタスビル | sofosbuvir/velpatasvir | SOF/VEL | エプクルーサ配合 | 核酸アナログ |
| ダクラタスビル | daclatasvir | DCV | ダクルインザ | HCV NS5A複製複合体阻害 |
| リバビリン | ribavirin | RBV | レベトール、コペガス | 核酸アナログ |
| レジパスビル・ソホスブビル | sofosbuvir/ledipasvir | SOF/LDV | ハーボニー配合 | HCV NS5A阻害・核酸アナログ |
| C型肝炎ウイルスの遺伝子型 | DAA治療歴のない慢性肝炎 | ||
| 一般名 | 備考 | ||
| 1型 | SOF/LDV | sofosbuvir/ledipasvir | 腎障害では禁 |
| EBR+GZR | elbasvir+grazoprevir | ||
| GLE/PIB | glecaprevir/pibrentasvir | ||
| 2型 | SOF+RBV | sofosbuvir+ribavirin | 腎障害では禁 |
| GLE/PIB | glecaprevir/pibrentasvir | ||
| SOF/LDV | sofosbuvir/ledipasvir | 腎障害では禁 | |
| C型肝炎ウイルスの遺伝子型 | DAA治療歴のない代償性肝硬変 | ||
| 一般名 | 備考 | ||
| 1型 | SOF/LDV | sofosbuvir/ledipasvir | 腎障害では禁 |
| EBR+GZR | elbasvir+grazoprevir | ||
| GLE/PIB | glecaprevir/pibrentasvir | ||
| 2型 | SOF+RBV | sofosbuvir+ribavirin | 腎障害では禁 |
| GLE/PIB | glecaprevir/pibrentasvir | ||
| SOF/LDV | sofosbuvir/ledipasvir | 腎障害では禁 | |
| B型肝炎 | C型肝炎 | ソース | |
| 感染の特徴 | 慢性の肝細胞障害、 integrationによる変異誘発？ |
慢性の肝細胞障害 | 根拠なし |
| 劇症化 | 0.1-1％ | 0.1％ | HIM |
| 慢性化率 | 1-10％ | 85％ | HIM |
| キャリア化 | 稀。通常、母子感染でおこる | 医学辞書 | |
| 肝細胞癌患者中 | 約20％ | 約70％ | QB.B-281 |
| 肝細胞癌患者年齢 | 若年発症 | QB.B-281 | |
| 肝細胞癌発症形式 | 突発あり | 緩徐進展 | QB.B-281 |
| 遺伝子型 | B型肝炎ウイルス#遺伝子型 | ||
| A型、C型 | 1b型、2a型,、2b型 | ||
| 日本ではC型多く、重症化しやすいが、慢性化しにくい。しかし、インターフェロン奏効しにくく、肝細胞癌発症しやすい。 | 日本では1b型多い。インターフェロン奏効しづらい(15%)。平均は2型は奏効しやすい(80%以上でウイルス排除) | ||
| 治療 | インターフェロン ラミブジン アデフォビル エンテカビル テルビブジン |
ペグインターフェロン＋リバビリン |