Hepcludex

/ Gilead Sciences Israel Ltd.

Recommended Dosage
Bulevirtide should be administered once daily by subcutaneous injection.
The recommended dosage in adults is Hepcludex 2 mg once daily, corresponding to a delivered dose of 1.7 mg.
Duration of treatment
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.
Mode of administration
For subcutaneous use only. Hepcludex may be administered into upper thigh or lower abdomen.
Missed dose
If a dose is missed, that dose should be taken as soon as possible on that day. However, if it is almost time for the next dose, skip the missed dose and go back to the regular dosing schedule. Do not double doses.

Treatment of chronic hepatitis delta virus (HDV) infection in plasma (or serum) HDV-RNA positive adult patients with compensated liver disease.

Hypersensitivity to the active substance or to any of the excipients

Exacerbation of hepatitis after discontinuation of treatment
Severe acute exacerbations of HDV and HBV infection may occur after Hepcludex is discontinued, especially in patients with cirrhosis, who may be at increased risk of more severe flares or progression to hepatic decompensation. Monitor hepatic function closely with both clinical and laboratory follow-up for several (at least six) months in patients who discontinue Hepcludex. In certain circumstances, resumption of antiviral therapy may be warranted.
Decompensated liver disease
The pharmacokinetics, safety and efficacy of Hepcludex in patients with decompensated cirrhosis have not been established. The use in patients with decompensated liver disease is not recommended.
Excipients
A 2 mg Hepcludex vial contains less than 1 mmol of sodium (23 mg) per injection, which means it is almost “sodium-free”.
See prescribing information for full details.

Very Common: headache, total bile salts increased, pruritus, injection site reactions
Common: eosinophilia, dizziness, nausea, fatigue

Effect of other agents on bulevirtide
NTCP inhibitors
In vitro, it has been shown that certain medicinal products can inhibit the therapeutic target molecule of bulevirtide, the sodium taurocholate co-transporting polypeptide (NTCP). The co-administration of such medicinal products (e.g. sulfasalazine, irbesartan, ezetimibe, ritonavir, and ciclosporine A) is not recommended.
Effect of bulevirtide on other agents
OATP1B1/3 and NTCP substrates
In vitro bulevirtide inhibited the organic anion transporting polypeptides, OATP1B1 and OATP1B3. A clinical drug drug interaction (DDI) study of bulevirtide (administered at 5 mg twice daily) showed a 1.34-fold increase of Cmax and AUC of the OATP1B1/3 and NTCP substrate, pravastatin (40 mg single dose). Based on bulevirtide exposures at the recommended 2 mg dose, the risk for clinically relevant interactions with OATP1B1/OATP1B3 and/or NTCP substrates is considered to be low. However, use with caution if OATP1B1/OATP1B3 and/or NTCP substrates (e.g. estrone-3-sulfate, fluvastatin, atorvastatin, pitavastatin, pravastatin, rosuvastatin, thyroid hormones, bosentan, docetaxel, fexofenadine, glecaprevir, glyburide (glibenclamide), grazoprevir, nateglinide, paclitaxel, repaglinide, simvastatin, olmesartan, telmisartan, valsartan and voxilaprevir) are administered in combination with bulevirtide.
CYP3A4 substrates
In clinical DDI studies, no strongly pronounced interaction effects of bulevirtide on the clearance of the CYP3A4 substrate midazolam were observed; however, weak interaction effects of bulevirtide on CYP3A4 substrates cannot be ruled out. As such, close monitoring is recommended as a precautionary measure if sensitive CYP3A4 substrates with a narrow therapeutic index (e.g. cyclosporine, carbamazepine, sirolimus and tacrolimus) are administered in combination with bulevirtide.
See prescribing information for full details.

Pregnancy: There are no or limited amount of data from the use of bulevirtide in pregnant women. As a precautious measure, it is preferable to avoid the use of bulevirtide during pregnancy and in women of child-bearing potential not using contraception.
Lactation: It is unknown whether bulevirtide is excreted in human milk. However, due to its high protein binding, bulevirtide is not likely to be secreted in milk. A decision must be made whether to breastfeed/discontinue breastfeeding or to discontinue / abstain from treatment with bulevirtide, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

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