bulevirtide acetate

HOS-098831 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile The most frequently reported adverse reactions are increase in bile salts (very common), headache (very common), pruritus (very common) and injection site reactions (very common). Increases in bile salts were usually asymptomatic and reversible upon treatment discontinuation. The most frequently reported serious adverse reaction is an exacerbation of hepatitis after discontinuation of bulevirtide, possibly related to virologic rebound after discontinuation of treatment (see section 4.4). Tabulated list of adverse reactions The following adverse reactions are based on pooled data from clinical studies in adults and post- marketing experience. Adverse reactions are listed below by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to, < 1/10), uncommon (≥ 1/1,000 to < 1/100). Frequency Adverse reaction Blood and lymphatic system disorders Common Eosinophilia Immune system disorders Uncommon Hypersensitivity, including anaphylactic reactiona Nervous system disorders Very common Headache Common Dizziness Gastrointestinal disorders Common Nausea Hepatobiliary disorders Very common Total bile salts increased Skin and subcutaneous tissue disorders Very common Pruritus Musculoskeletal and connective tissue disorders Common Arthralgia General disorders and administration site conditions Very common Injection site reactionsb Common Fatigue Common Influenza like illness a Adverse reaction identified through post-marketing surveillance b Includes injection site erythema, injection site reaction, injection site pain, injection site induration, injection site swelling, injection site rash, injection site haematoma, injection site pruritus and injection site dermatitis Description of selected adverse reactions Total Bile Salts Increased Asymptomatic bile salt elevations, associated with the mechanism of action of bulevirtide, were very commonly observed in clinical studie

Auszug; vollständigen Abschnitt im Original lesen.

HOS-098827 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098826 · has-indication-information · PDF-Seite 2

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.

HOS-098829 · has-interaction-information · PDF-Seite 4

In vitro, it has been shown, that certain medicinal products can inhibit bulevirtide target sodium- taurocholate co-transporting polypeptide (NTCP). The co-administration of such medicinal products (e.g. sulfasalazin, irbesartan, ezetimibe, ritonavir, and ciclosporin A) is not recommended. 4 As a precautionary measure, close clinical monitoring is warranted when NTCP substrates (e.g. estrone-3-sulfate, fluvastatin, atorvastatin, pitavastatin, pravastatin, rosuvastatin, and thyroid hormones) are co-administered with bulevirtide. When possible, co-administration of these substrates should be avoided. In vitro an inhibition of OATP1B1/3 transporters by bulevirtide was observed, albeit only at a concentration ≥ 0.5 µM, which is only reached in vivo after administration of high bulevirtide doses (10 mg subcutaneous). The clinical relevance of these findings is unknown. As a precautionary measure, close clinical monitoring is warranted when OATP1B1/3 substrates (e.g. atorvastatin, bosentan, docetaxel, fexofenadine, glecaprevir, glyburide (glibenclamide), grazoprevir, nateglinide, paclitaxel, paritaprevir, pitavastatin, pravastatin, repaglinide, rosuvastatin, simeprevir, simvastatin, olmesartan, telmisartan, valsartan, voxilaprevir) are co-administered. When possible, co- administration of these substrates should be avoided. In a clinical study in healthy subjects, co-administration of tenofovir and bulevirtide revealed no impact on tenofovir pharmacokinetics. No CYP inhibition by bulevirtide was observed in vitro at clinically relevant concentrations. However, in a clinical study, an approximately 40% increase in geometric mean of partial AUC2-4h values of co-administered midazolam (CYP3A4 substrate) was observed in combination of high dose bulevirtide (10 mg) and tenofovir (245 mg), whereas no significant influence on midazolam AUC2-4h was detected for tenofovir alone. As a precautionary measure, close clinical monitoring is warranted for co-administered narrow-therapeutic-index drugs which are sensitive CYP3A4 substrates (e.g. cyclosporine, carbamazepine, simvastatin, sirolimus, and tacrolimus).

HOS-098830 · has-pregnancy-information · PDF-Seite 5

Pregnancy There are no or limited amount of data from the use of bulevirtide in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. 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. Breast-feeding It is unknown whether bulevirtide is excreted in human milk. Therefore, a decision must be made whether to discontinue breast-feeding or to discontinue / abstain from treatment with bulevirtide, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility No human data on the effect of bulevirtide on fertility are available. In animal studies, no effects of bulevirtide on male or female mating and fertility were noted.

HOS-098828 · has-warning-information · PDF-Seite 4

HDV and HBV genotype HDV genotype 1 was predominant in the clinical trials population. It is not known whether HDV or HBV genotype affects the clinical efficacy of bulevirtide. Decompensated liver disease The pharmacokinetics, safety and efficacy of bulevirtide in patients with decompensated cirrhosis has not been established. The use in patients with decompensated liver disease is not recommended. Co-infection with HBV The underlying HBV infection should be simultaneously managed according to current treatment guidelines. In the clinical study of bulevirtide MYR202, only patients with signs of active hepatitis despite nucleoside/nucleotide analogue treatment were included; tenofovir disoproxil fumarate was co- administered with bulevirtide. Close monitoring of HBV DNA levels is recommended. Hepatitis exacerbations after treatment cessation Discontinuation of treatment with bulevirtide may lead to reactivation of HDV and HBV infections and severe acute exacerbations of hepatitis, especially in patients with cirrhosis who may be at increased risk of more severe flares or progression to hepatic decompensation. In case of treatment discontinuation, careful monitoring of hepatic function with both clinical and laboratory follow-up should be performed for at least 6 months after discontinuation, including monitoring transaminase levels, as well as HBV DNA and HDV RNA viral load. In certain circumstances, resumption of antiviral therapy may be warranted. Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) No data are available from HIV or HCV co-infected patients. Excipients This medicine contains less than 1 mmol of sodium (23 mg) per ml, that is to say essentially "sodium-free".