REBETOL Hard capsule Ref.[8114] Active ingredients: Ribavirin

Treatment should be initiated, and monitored, by a physician experienced in the management of chronic hepatitis C.

Posology

Rebetol must be used in combination therapy as described in section 4.1. Please refer to the corresponding Summary of Product Characteristics (SmPC) of medicinal products used in combination with Rebetol for additional prescribing information particular to that product and for further dosage recommendations on co-administration with Rebetol.

Rebetol capsules are to be administered orally each day in two divided doses (morning and evening) with food.

Adults

The recommended dose and duration of Rebetol depends on patient’s weight and on the medicinal product that is used in combination. Please refer to the corresponding SmPC of medicinal products used in combination with Rebetol.

In the cases in which no specific dose recommendation is made, the following dose should be used: Patient weight: <75 kg =1,000 mg and >75 kg = 1,200 mg.

Paediatric population

No data are available in children below 3 years of age.

Note: For patients who weigh <47 kg, or are unable to swallow capsules, please refer to the SmPC for Rebetol 40 mg/mL oral solution.

Dosing of Rebetol for children and adolescent patients is determined by the patient body weight. For example, the body weight dosing used in conjunction with interferon alfa-2b or peginterferon alfa-2b is shown in Table 1. Please refer to the corresponding SmPC of medicinal products used in combination with Rebetol as some combination regimens do not adhere to the Rebetol dosing guidance provided in Table 1.

Table 1. Rebetol dose based on body weight when used in combination with interferon alfa-2b or peginterferon alfa-2b in paediatric patients:

^a 1 morning, 2 evening
^b 2 morning, 2 evening

Dose modification for adverse reactions

Dose modification for adults

Dose reduction of Rebetol depends on the initial Rebetol posology which depends on the medicinal product that is used in combination with Rebetol.

If a patient has a serious adverse reaction potentially related to Rebetol, the Rebetol dose should be modified or discontinued, if appropriate, until the adverse reaction abates or decreases in severity.

Table 2 provides guidelines for dose modifications and discontinuation based on the patient’s haemoglobin concentration, cardiac status and indirect bilirubin concentration.

Table 2. Management of Adverse Reactions:

* For patients receiving a 1,000 mg (<75 kg) or 1,200 mg (>75 kg) dose, Rebetol dose should be reduced to 600 mg/day (administered as one 200 mg capsule in the morning and two 200 mg capsules in the evening). If the abnormality is reversed, Rebetol may be restarted at 600 mg daily, and further increased to 800 mg daily at the discretion of the treating physician. However, a return to higher doses is not recommended.

For patients receiving a 800 mg (<65 kg)-1,000 mg (65-80 kg)-1,200 mg (81-105 kg) or 1,400 mg (>105 kg) dose, 1st dose reduction of Rebetol is by 200 mg/day (except in patients receiving the 1,400 mg, dose reduction should be by 400 mg/day). If needed, 2nd dose reduction of Rebetol is by an additional 200 mg/day. Patients whose dose of Rebetol is reduced to 600 mg daily receive one 200 mg capsule in the morning and two 200 mg capsules in the evening.

In case of serious adverse reaction potentially related to medicinal products used in combination with Rebetol, refer to the corresponding SmPC of these medicinal products as some combination regimens do not adhere to the Rebetol dose modification and/or discontinuation guidelines as described in Table 2.

Dose modification for paediatric patients

Dose reduction in paediatric patients without cardiac disease follows the same guidelines as adult patients without cardiac disease regarding haemoglobin levels (Table 2).

There are no data for paediatric patients with cardiac disease (see section 4.4).

Table 3 provides guidelines for discontinuation based on the patient’s indirect bilirubin concentration.

Table 3. Management of Adverse Reactions:

Special populations

Elderly (≥65 years of age)

There does not appear to be a significant age-related effect on the pharmacokinetics of Rebetol. However, as in younger patients, renal function must be determined prior to administration of Rebetol (see section 5.2).

Paediatric patients (children 3 years of age and older and adolescents)

Rebetol may be used in combination with peginterferon alfa-2b or interferon alfa-2b (see section 4.4). The selection of Rebetol formulation is based on individual characteristics of the patient. The safety and efficacy of ribavirin used together with direct-acting-anti-virals in these patients has not been established. No data are available.

Please refer to the corresponding SmPC of medicinal products used in combination with Rebetol for further dosage recommendations on co-administration.

Renal impairment

The pharmacokinetics of Rebetol is altered in patients with renal dysfunction due to reduction of apparent creatinine clearance in these patients (see section 5.2). Therefore, it is recommended that renal function be evaluated in all patients prior to initiation of Rebetol. Adult patients with moderate renal impairment (creatinine clearance of 30-50 mL/minute) should be administered alternating daily doses of 200 mg and 400 mg. Adult patients with severe renal impairment (creatinine clearance of <30 mL/minute) and patients with End Stage Renal Disease (ESRD) or on haemodialysis should be administered Rebetol 200 mg/day. Table 4 provides guidelines for dose modification for patients with renal dysfunction. Patients with impaired renal function should be more carefully monitored with respect to the development of anaemia. No data are available regarding dose modification for paediatric patients with renal impairment.

Table 4. Dosage Modification for Renal Impairment in Adult Patients:

Hepatic impairment

No pharmacokinetic interaction appears between Rebetol and hepatic function (see section 5.2). For use in patients with decompensated cirrhosis, see the corresponding SmPC of the medicinal products used in combination with Rebetol.

Method of administration

Rebetol should be administered orally with food.

In clinical trials with Rebetol used in combination with peginterferon alfa-2b or interferon alfa-2b, the maximum overdose reported was a total dose of 10 g of Rebetol (50 × 200 mg capsules) and 39 MIU of interferon alfa-2b (13 subcutaneous injections of 3 MIU each) taken in one day by a patient in an attempt at suicide. The patient was observed for two days in the emergency room, during which time no adverse reaction from the overdose was noted.

Shelf life: 2 years.

Do not store above 30°C.

Rebetol capsules are packaged in blisters consisting of polyvinyl chloride (PVC)/polyethylene (PE)/polyvinylidene chloride (PVdC).

Packs of 84, 112, 140 and 168 capsules.

Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.