Drug Detail:Harvoni (Ledipasvir and sofosbuvir [ le-dip-as-vir-and-soe-fos-bue-vir ])
Generic Name: LEDIPASVIR 90mg, SOFOSBUVIR 400mg
Dosage Form: tablet, film coated
Drug Class: Antiviral combinations
Testing Prior to the Initiation of Therapy
Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with HARVONI [see Warnings and Precautions (5.1)].
Recommended Treatment Regimen and Duration in Patients 3 Years of Age and Older with Genotype 1, 4, 5, or 6 HCV
Table 1 shows the recommended HARVONI treatment regimen and duration based on patient population. Relapse rates are affected by baseline host and viral factors and differ between treatment durations for certain subgroups [see Clinical Studies (14)].
For patients with HCV/HIV-1 coinfection, follow the dosage recommendations in Table 1 [see Clinical Studies (14)]. Refer to Drug Interactions (7) for dosage recommendations for concomitant HIV-1 antiviral drugs.
| HCV Genotype | Patient Population | Treatment Regimen and Duration |
|---|---|---|
|
||
| Genotype 1 | Treatment-naïve without cirrhosis or with compensated cirrhosis (Child-Pugh A) | HARVONI 12 weeks* |
| Treatment-experienced† without cirrhosis | HARVONI 12 weeks | |
| Treatment-experienced† with compensated cirrhosis (Child-Pugh A) | HARVONI 24 weeks‡ | |
| Treatment-naïve and treatment-experienced† with decompensated cirrhosis (Child-Pugh B or C) | HARVONI + ribavirin§ 12 weeks | |
| Genotype 1 or 4 | Treatment-naïve and treatment-experienced† liver transplant recipients without cirrhosis, or with compensated cirrhosis (Child-Pugh A) | HARVONI + ribavirin§ 12 weeks |
| Genotype 4, 5, or 6 | Treatment-naïve and treatment-experienced†, without cirrhosis or with compensated cirrhosis (Child-Pugh A) | HARVONI 12 weeks |
Recommended Dosage in Adults
The recommended dosage of HARVONI in adults with genotype 1, 4, 5, or 6 HCV is one tablet (90 mg ledipasvir and 400 mg sofosbuvir) taken orally once daily with or without food [see Clinical Pharmacology (12.3)].
The daily dosage of ribavirin is weight-based (1000 mg for patients <75 kg and 1200 mg for those ≥75 kg) administered orally in two divided doses with food.
In patients with decompensated cirrhosis, the starting dosage of ribavirin is 600 mg and can be titrated up to 1000 mg for patients <75 kg and 1200 mg for those ≥75 kg in two divided doses with food. If the starting dosage of ribavirin is not well tolerated, the dosage should be reduced as clinically indicated based on hemoglobin levels.
For further information on ribavirin dosing and dosage modifications, refer to the ribavirin prescribing information [see Dosage and Administration (2.4), Use in Specific Populations (8.6), and Clinical Studies (14.5)].
Recommended Dosage in Pediatric Patients 3 Years of Age and Older
The recommended dosage of HARVONI in pediatric patients 3 years of age and older with genotype 1, 4, 5, or 6 HCV using HARVONI tablets or oral pellets is based on weight (Table 2). Table 3 provides the weight-based dosage of ribavirin when used in combination with HARVONI for pediatric patients. Take HARVONI tablets or pellets (with or without food) once daily [see Dosage and Administration (2.5), Clinical Pharmacology (12.3), and Clinical Studies (14.7)]. HARVONI pellets can be taken in pediatric patients who cannot swallow the tablet formulation.
| Body Weight (kg) | Dosing of HARVONI Tablets or Oral Pellets | HARVONI Daily Dose |
|---|---|---|
| at least 35 | one 90 mg/400 mg tablet once daily or two 45 mg/200 mg tablets once daily or two 45 mg/200 mg packets of pellets once daily |
90 mg/400 mg per day |
| 17 to less than 35 | one 45 mg/200 mg tablet once daily or one 45 mg/200 mg packet of pellets once daily |
45 mg/200 mg per day |
| less than17 | one 33.75 mg/150 mg packet of pellets once daily | 33.75 mg/150 mg per day |
| Body Weight (kg) | Oral Ribavirin Daily Dosage* |
|---|---|
|
|
| less than 47 | 15 mg per kg per day (divided dose AM and PM) |
| 47–49 | 600 mg per day (1 × 200 mg AM, 2 × 200 mg PM) |
| 50–65 | 800 mg per day (2 × 200 mg AM, 2 × 200 mg PM) |
| 66–80 | 1000 mg per day (2 × 200 mg AM, 3 × 200 mg PM) |
| greater than 80 | 1200 mg per day (3 × 200 mg AM, 3 × 200 mg PM) |
Preparation and Administration of Oral Pellets
See the HARVONI oral pellets full Instructions for Use for details on the preparation and administration of HARVONI pellets.
Do not chew HARVONI pellets. If HARVONI pellets are administered with food, sprinkle the pellets on one or more spoonfuls of non-acidic soft food at or below room temperature. Examples of non-acidic foods include pudding, chocolate syrup, mashed potato, and ice cream. Take HARVONI pellets within 30 minutes of gently mixing with food and swallow the entire contents without chewing to avoid a bitter aftertaste.
Renal Impairment
No dosage adjustment of HARVONI is recommended in patients with any degree of renal impairment, including end stage renal disease (ESRD) on dialysis [see Dosage and Administration (2.3)]. Take HARVONI with or without ribavirin according to the recommendations in Table 1 [see Adverse Reactions (6.1), Use in Specific Populations (8.6), and Clinical Studies (14.6)]. Refer to ribavirin tablet prescribing information for ribavirin dosage modification for patients with CrCl less than or equal to 50 mL per minute.
