SOLEDIVIR

SOLEDIVIR
Packing4 blister packs of 7 tablets/1 bottle of 28 tablets
Shelf life36 months
CompositionSofosbuvir 400 mg and Ledipasvir 90 mg
Posology and pharmaceutical formFilm-coated tablet

Summary of product characteristic

Indications, posology and method of administration

THERAPEUTIC INDICATIONS
Soledivir is indicated for the treatment of chronic hepatitis C (CHC) in adult and adolescents aged 12 to < 18 years.
For specific genotypes of the hepatitis C virus (HCV), refer to the pharmacodynamics section.
POSOLOGY AND METHOD OF ADMINISTRATION
Soledivir treatment should be initiated and monitored by a physician experienced in the management of patients with CHC.
Posology
Adult and adolescents aged 12 to < 18 years
The recommended dose of Soledivir in adults is 90 mg/400 mg once daily with or without food.
Table 1: Recommended treatment duration for Soledivir and the recommended use of co-administered ribavirin for certain subgroups

Patient population (including HIV co-infected patients)	Treatment and duration
Patients with genotype 1, 4, 5 or 6 CHC
Patients without cirrhosis	Soledivir for 12 weeks. - Soledivir for 8 weeks may be considered in previously untreated genotype 1-infected patients.
Patients with compensated cirrhosis	Soledivir + ribavirinA for 12 weeks or Soledivir (without ribavirin) for 24 weeks. - Soledivir (without ribavirin) for 12 weeks may be considered for patients deemed at low risk for clinical disease progression and who have subsequent retreatment options.
Patients who are post-liver transplant without cirrhosis or with compensated cirrhosis	Soledivir + ribavirinA for 12 weeks. - Soledivir (without ribavirin) for 12 weeks (in patients without cirrhosis) or 24 weeks (in patients with cirrhosis) may be considered for patients who are ineligible for or intolerant to ribavirin.
Patients with decompensated cirrhosis irrespective of transplant status	Soledivir + ribavirinB for 12 weeks. - Soledivir (without ribavirin) for 24 weeks may be considered in patients who are ineligible for or intolerant to ribavirin.
Patients with genotype 3 CHC
Patients with decompensated cirrhosis and/or liver failure prior to treatment.	Soledivir + ribavirinA for 24 weeks.

AAdults: The daily dose of ribavirin is weight-based (< 75 kg = 1,000 mg and ≥ 75 kg = 1,200 mg), administered orally in two divided doses with food. Adolescents: The recommended dose is provided in Table 3.
BFor ribavirin dosing recommendations in patients with decompensated cirrhosis, see Table 2.
Table 2: Guidance for ribavirin dosing when administered with Soledivir to patients with decompensated cirrhosis

Patient	Ribavirin dose*
Child-Pugh-Turcotte (CPT) Class B cirrhosis pre-transplant	1,000 mg per day for patients < 75 kg and 1,200 mg for those weighing ≥ 75 kg
CPT Class C cirrhosis pre-transplant CPT Class B or C cirrhosis post- transplant	Starting dose of 600 mg, which can be titrated up to a maximum of 1,000/1,200 mg (1,000 mg for patients weighing < 75 kg and 1,200 mg for patients weighing ≥ 75 kg) if well tolerated. If the starting dose is not well tolerated, the dose should be reduced as clinically indicated based on haemoglobin levels

* If a more normalized dose of ribavirin (by weight and renal function) cannot be reached for reasons of tolerability, 24 weeks of Soledivir + ribavirin should be considered in order to minimize the risk for relapse.
When ribavirin is used in combination with Soledivir, refer to the ribavirin prescribing information.
For adolescents aged 12 to < 18 years, the recommended ribavirin dose is divided into two daily doses and given with food:
Table 3: Guidance for ribavirin dosing when administered with Soledivir to adolescents aged 12 to < 18 years.

Body weight kg	Ribavirin Dose*
< 47	15 mg/kg/day
47 – 49	600 mg/day
50 – 65	800 mg/day
66 – 74	1000 mg/day
> or = 75	1200 mg/day

* The daily dosage of ribavirin is weight-based and administered orally in two divided doses with food.
Dose modification of ribavirin in adults taking 1,000 – 1,200 mg daily
If Soledivir is used in combination with ribavirin and a patient has a serious adverse reaction potentially related to ribavirin, the ribavirin dose should be modified or discontinued. Table 4 provides guidelines for dose modifications and discontinuation based on the patient's haemoglobin concentration and cardiac status.
Table 4: Ribavirin dose modification guideline for co-administration with Soledivir in adults

Laboratory values	Reduce ribavirin dose to 600 mg/day if:	Discontinue ribavirin if:
Haemoglobin in patients with no cardiac disease	< 10 g/dL	< 8.5 g/dL
Haemoglobin in patients with history of stable cardiac disease	≥ 2 g/dL decrease in haemoglobin during any 4-week treatment period	< 12 g/dL despite 4 weeks at reduced dose

Once ribavirin has been withheld due to either a laboratory abnormality or clinical manifestation, an attempt may be made to restart ribavirin at 600 mg daily and further increase the dose to 800 mg daily. However, it is not recommended that ribavirin be increased to the originally assigned dose (1,000 mg to 1,200 mg daily).
Paediatric population aged < 12 years
The safety and efficacy of Soledivir in paediatric patients aged < 12 years have not been established. No data areavailable.
Missed dose
Patients should be instructed that if vomiting occurs within 5 hours of dosing an additional tablet should be taken. If vomiting occurs more than 5 hours after dosing, no further dose is needed.
If a dose is missed and it is within 18 hours of the normal time, patients should be instructed to take the tablet as soon aspossible and then patients should take the next dose at the usual time. If it is after 18 hours then patients should be instructed to wait and take the next dose at the usual time. Patients should be instructed not to take a double dose.
Elderly
No dose adjustment is warranted for elderly patients.
Renal impairment
No dose adjustment of Soledivir is required for patients with mild or moderate renal impairment.
Safety data are limited in patients with severe renal impairment (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m2) and end stage renal disease (ESRD) requiring dialysis. Treatment with ledipasvir/sofosbuvir should not be used in patients with severe renal impairment or end-stage renal disease, and is only recommended when alternative treatment regimens are not available.
Hepatic impairment
No dose adjustment of Soledivir is required for patients with mild, moderate or severe hepatic impairment (Child-Pugh-Turcotte [CPT] class A, B or C). Safety and efficacy of ledipasvir/sofosbuvir have been established in patients with decompensated cirrhosis.
Method of administration
For oral use.
It may be given with or without food. Due to the bitter taste, it is recommended that film-coated tablets are not chewed or crushed.
CONTRAINDICATIONS
Hypersensitivity to the active substance or to any of the excipients.
Concurrent use with rosuvastatin.
Use with strong P-gp inducers:
Medicinal products that are strong P-glycoprotein (P-gp) inducers in the intestine (rifampicin, rifabutin, St. John’s wort [Hypericum perforatum], carbamazepine, phenobarbital và phenytoin). Co-administration will significantly decrease ledipasvir and sofosbuvir plasma concentrations and could result in loss of efficacy of Soledivir.

THERAPEUTIC INDICATIONS
Soledivir is indicated for the treatment of chronic hepatitis C (CHC) in adult and adolescents aged 12 to < 18 years.
For specific genotypes of the hepatitis C virus (HCV), refer to the pharmacodynamics section.
POSOLOGY AND METHOD OF ADMINISTRATION
Soledivir treatment should be initiated and monitored by a physician experienced in the management of patients with CHC.
Posology
Adult and adolescents aged 12 to < 18 years
The recommended dose of Soledivir in adults is 90 mg/400 mg once daily with or without food.
Table 1: Recommended treatment duration for Soledivir and the recommended use of co-administered ribavirin for certain subgroups

Patient population (including HIV co-infected patients)	Treatment and duration
Patients with genotype 1, 4, 5 or 6 CHC
Patients without cirrhosis	Soledivir for 12 weeks. - Soledivir for 8 weeks may be considered in previously untreated genotype 1-infected patients.
Patients with compensated cirrhosis	Soledivir + ribavirinA for 12 weeks or Soledivir (without ribavirin) for 24 weeks. - Soledivir (without ribavirin) for 12 weeks may be considered for patients deemed at low risk for clinical disease progression and who have subsequent retreatment options.
Patients who are post-liver transplant without cirrhosis or with compensated cirrhosis	Soledivir + ribavirinA for 12 weeks. - Soledivir (without ribavirin) for 12 weeks (in patients without cirrhosis) or 24 weeks (in patients with cirrhosis) may be considered for patients who are ineligible for or intolerant to ribavirin.
Patients with decompensated cirrhosis irrespective of transplant status	Soledivir + ribavirinB for 12 weeks. - Soledivir (without ribavirin) for 24 weeks may be considered in patients who are ineligible for or intolerant to ribavirin.
Patients with genotype 3 CHC
Patients with decompensated cirrhosis and/or liver failure prior to treatment.	Soledivir + ribavirinA for 24 weeks.

Patient	Ribavirin dose*
Child-Pugh-Turcotte (CPT) Class B cirrhosis pre-transplant	1,000 mg per day for patients < 75 kg and 1,200 mg for those weighing ≥ 75 kg
CPT Class C cirrhosis pre-transplant CPT Class B or C cirrhosis post- transplant	Starting dose of 600 mg, which can be titrated up to a maximum of 1,000/1,200 mg (1,000 mg for patients weighing < 75 kg and 1,200 mg for patients weighing ≥ 75 kg) if well tolerated. If the starting dose is not well tolerated, the dose should be reduced as clinically indicated based on haemoglobin levels

Body weight kg	Ribavirin Dose*
< 47	15 mg/kg/day
47 – 49	600 mg/day
50 – 65	800 mg/day
66 – 74	1000 mg/day
> or = 75	1200 mg/day

Laboratory values	Reduce ribavirin dose to 600 mg/day if:	Discontinue ribavirin if:
Haemoglobin in patients with no cardiac disease	< 10 g/dL	< 8.5 g/dL
Haemoglobin in patients with history of stable cardiac disease	≥ 2 g/dL decrease in haemoglobin during any 4-week treatment period	< 12 g/dL despite 4 weeks at reduced dose

This information is for reference only. Please read the leaflet inside.

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