Source: European Medicines Agency (EU) Revision Year: 2024 Publisher: Gilead Sciences Ireland UC, Carrigtohill, County Cork, T45 DP77, Ireland
Hepcludex is indicated for the treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult and paediatric patients 3 years of age and older weighing at least 10 kg with compensated liver disease.
Treatment should be initiated only by a physician experienced in the treatment of patients with HDV infection.
Bulevirtide should be administered once daily (every 24 hours ± 4 hours) by subcutaneous injection as monotherapy or in co-administration with a nucleoside/nucleotide analogue for treatment of underlying hepatitis B virus (HBV) infection.
The recommended dose of bulevirtide in adult patients is 2 mg once daily.
The recommended dose of bulevirtide in paediatric patients is based on weight as detailed in the Table below.
Dosing for paediatric patients using bulevirtide 2 mg powder for solution for injection:
| Body Weight (kg) | Dosing of reconstituted bulevirtide 2 mg powder for solution for injection (ml) | Bulevirtide Daily Dose |
|---|---|---|
| 10 kg to <25 kg | 0.5 ml | 1 mg |
| 25 kg to <35 kg | 0.75 ml | 1.5 mg |
| 35 kg and above | 1 ml | 2 mg |
Concerning co-administration with nucleoside-nucleotide analogues for treatment of HBV infection, refer to section 4.4.
The optimal treatment duration is unknown. Treatment should be continued as long as associated with clinical benefit.
Consideration to discontinue the treatment should be given in case of sustained (6 months) HBsAg seroconversion or loss of virological and biochemical response.
If an injection has been omitted and less than 4 hours have elapsed since the scheduled time, the injection must be performed as soon as possible. The time of the next injection will not be calculated from the time of the “rescue” injection, but according to the injection schedule previously established. It is, therefore, necessary to return to the usual pattern of administration, at the appointed time, the following day.
If an injection has been missed and more than 4 hours have elapsed since the scheduled time, the missed dose should not be administered.
The next injection will take place according to the usual schedule (injection of the prescribed dose without doubling), at the appointed time the next day.
If the injection has been made by mistake more than 4 hours after the scheduled time, the next administration must take place in the usual way (i.e. in accordance with the original schedule).
No data is available in patients >65 years.
No studies have been conducted with bulevirtide in patients with renal impairment. Renal function should be carefully monitored. Elevation of bile salts may occur during treatment. Due to renal excretion of bile salts, elevation of bile salts may be greater in patients with renal impairment.
No dose adjustment is required for patients with mild hepatic impairment (Child-Pugh-Turcotte class A). The safety and efficacy of bulevirtide in patients with decompensated cirrhosis have not been established (see sections 4.4 and 5.2).
The safety and efficacy of bulevirtide in patients younger than 18 years of age have not been established in clinical studies. The recommended dosage of bulevirtide for paediatric patients 3 years of age and older weighing at least 10 kg with compensated liver disease is based on population pharmacokinetic/pharmacodynamic modelling and simulation (see section 5.2).
For subcutaneous use only. Bulevirtide may be injected into sites such as the upper thigh, or abdomen. Appropriate training should be given to the patients self-administering the product or to the caregivers administering the product to minimise the risk of the injection site reactions.
The “Step-by-step injection guide”, provided in the carton, must be followed carefully by the patient or the caregiver.
For instructions on reconstitution of the medicinal product before administration, see section 6.6.
There are no data on human overdose with bulevirtide. If overdose occurs, the patient must be monitored for evidence of toxicity and given standard supportive treatment as necessary.
2 years.
After reconstitution, chemical and physical in-use stability has been demonstrated for 2 hours at room temperature (up to 25°C). From a microbiological point of view, it is recommended that the product should be used immediately.
Store in a refrigerator (2°C-8°C). In order to protect from light, keep the vials in the outer carton.
Colourless glass vial with bromobutyl or chlorobutyl rubber stopper, sealed with a flip off cap (aluminium with plastic disc).
Pack-size of 30 vials.
Each vial is intended for single use only and the excess of unused product must be properly disposed of. Sterile water for injections, syringes (with necessary graduations according to the dose to be administered), needle tips and alcohol wipes should be provided to the patient.
The bulevirtide vial should be taken from the refrigerator shortly before the injection and the blue flip- off cap has to be removed. A single-use syringe should be taken and a needle tip attached to the syringe head in order to extract 1 ml of sterile water for injection into the syringe. The syringe needle with the syringe containing the sterile water for injection should then be inserted into the bulevirtide vial through the rubber stopper. The sterile water for injection inside the syringe will then be injected into the bulevirtide vial and the bulevirtide vial has to be carefully swayed until a clear solution is obtained. The required content for the dose to be administered from the bulevirtide vial has to be extracted back into the same syringe with the same needle tip (See Table below).
Required dose volumes to be extracted for administration of bulevirtide:
| Bulevirtide Dose | Required volume of reconstituted bulevirtide to be extracted |
|---|---|
| 1 mg | 0.5 ml |
| 1.5 mg | 0.75 ml |
| 2 mg | 1 ml |
The needle tip has then to be detached from the syringe. To this syringe, a needle tip for subcutaneous injection has to be attached and any remaining air bubbles have to be removed from the syringe prior to injection. The content of the bulevirtide vial will then be administered subcutaneously.
All used components/waste should be handled according to the current regulation.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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