HEPATITIS C MEDICINE IN INDIA

Each film-coated tablet Contains:

Ledipasvir 90 mg

Sofosbuvir 400 mg

Colors: Yellow oxide of Iron, Titanium Dioxide IP and FD&C Blue#2

Ledikast is a fixed-dose combination tablet containing ledipasvir and sofosbuvir for oral administration. Ledipasvir is an HCV NS5A inhibitor and sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase.

Each film-coated tablet contains 90 mg ledipasvir and 400 mg sofosbuvir. The tablet includes the following inactive ingredients: colloidal silicon dioxide, copovidone, croscarmellose sodium, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. The tablet is film-coated with a coating material containing the following inactive ingredients: Yellow Oxide of Iron, polyethylene glycol, polyvinyl alcohol, talc, FD&C Blue #2 and titanium dioxide IP.

Ledipasvir: The IUPAC name for ledipasvir is Methyl [(2S)-1-{(6S)-6-[5-(9,9-difluoro-7-{2-[(1R,3S,4S)-2-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-2azabicyclo[2.2.1] hept-3-yl]-1H-benzimidazol-6-yl}-9H-fluoren-2-yl)-1H-imidazol-2-yl]-5-azaspiro[2.4] hept-5-yl}-3-methyl-1-oxobutan-2-yl]carbamate.

2.0 CLINICAL PHARMACOLOGY

2.1 Mechanism of Action

Ledikast is a fixed-dose combination of ledipasvir and sofosbuvir which are directacting antiviral agents against the hepatitis C virus.

2.2 Pharmacodynamics

Cardiac Electrophysiology

Ledipasvir at a dose of 120 mg twice daily (2.67 times the maximum recommended dosage) and sofosbuvir 400 mg (maximum recommended dosage) and 1200 mg (three times the maximum recommended dosage) does not prolong QTc in clinical trials.

ADVERSE REACTIONS

9.1 Clinical Trials Experience

The most common adverse reactions (≥10%) were fatigue and headache in subjects treated with 8, 12, or 24 weeks of Ledikast. Table 2 lists adverse reactions (adverse events assessed as causally related by the investigator, all grades) observed in ≥5% of subjects receiving 8, 12, or 24 weeks treatment with Ledipasvir + Sofosbuvir in clinical trials. The majority of adverse reactions presented in Table 2 occurred at severity of grade 1. The side-by-side tabulation is to simplify presentation; direct comparison across trials should not be made due to differing trial designs.

Drugs without Clinically Significant Interactions with Ledikast

Based on drug interaction studies conducted with individual drugs Ledipasvir or Sofosbuvir or combination of Ledipasvir + Sofosbuvir, no clinically significant drug interactions have either been observed or are expected when Ledipasvir + Sofosbuvir is used with the following drugs individually: abacavir, atazanavir/ritonavir, cyclosporine, darunavir/ ritonavir, efavirenz, emtricitabine, lamivudine, , oral contraceptives, pravastatin, raltegravir, rilpivirine, tacrolimus, tenofovir disoproxil fumarate, or verapamil. See Table 3 for use of Ledikast with certain HIV antiretroviral regimens.

12.0 OVERDOSAGE

No specific antidote is available for overdose with Ledikast. If overdose occurs the patient must be monitored for evidence of toxicity. Treatment of overdose with Ledikast consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient. Hemodialysis is unlikely to result in significant removal of ledipasvir since ledipasvir is highly bound to plasma protein. Hemodialysis can efficiently remove the predominant circulating metabolite of sofosbuvir, GS-331007, with an extraction ratio of 53%.

13.0 HOW SUPPLIED/STORAGE AND HANDLING

Ledikast tablets are Green colored, oval shaped and film-coated. 28 tablets packed in a bottle. One bottle and one literature housed in a carton.

Store below 30°C.

• Delivery Time: 1 To 2 Days