Vemlidy 25 mg film-coated tablets.

Each film-coated tablet contains tenofovir alafenamide fumarate equivalent to 25 mg of tenofovir alafenamide.

Excipient with known effect

Each tablet contains 95 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

Film-coated tablet.

Yellow, round, film-coated tablets, 8 mm in diameter, debossed with “GSI” on one side of the tablet and “25” on the other side of the tablet.

Vemlidy is indicated for the treatment of chronic hepatitis B in adults and adolescents (aged 12 years and older with body weight at least 35 kg) (see section 5.1).

Therapy should be initiated by a physician experienced in the management of chronic hepatitis B.

Posology

Adults and adolescents (aged 12 years and older with body weight at least 35 kg): one tablet once daily.

Treatment discontinuation

Treatment discontinuation may be considered as follows (see section 4.4):

• In HBeAg-positive patients without cirrhosis, treatment should be administered for at least 6-12 months after HBe seroconversion (HBeAg loss and HBV DNA loss with anti-HBe detection) is confirmed or until HBs seroconversion or until there is loss of efficacy (see section 4.4). Regular reassessment is recommended after treatment discontinuation to detect virological relapse.

• In HBeAg-negative patients without cirrhosis, treatment should be administered at least until HBs seroconversion or until there is evidence of loss of efficacy. With prolonged treatment for more than 2 years, regular reassessment is recommended to confirm that continuing the selected therapy remains appropriate for the patient.

Missed dose

If a dose is missed and less than 18 hours have passed from the time it is usually taken, the patient should take Vemlidy as soon as possible and then resume their normal dosing schedule. If more than 18 hours have passed from the time it is usually taken, the patient should not take the missed dose and should simply resume the normal dosing schedule.

If the patient vomits within 1 hour of taking Vemlidy, the patient should take another tablet. If the patient vomits more than 1 hour after taking Vemlidy, the patient does not need to take another tablet.

Special populations

Elderly

No dose adjustment of Vemlidy is required in patients aged 65 years and older (see section 5.2).

Renal impairment

No dose adjustment of Vemlidy is required in adults or adolescents (aged at least 12 years and of at least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 15 mL/min or in patients with CrCl < 15 mL/min who are receiving haemodialysis.

On days of haemodialysis, Vemlidy should be administered after completion of haemodialysis treatment (see section 5.2).

No dosing recommendations can be given for patients with CrCl < 15 mL/min who are not receiving haemodialysis (see section 4.4).

Hepatic impairment

No dose adjustment of Vemlidy is required in patients with hepatic impairment (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of Vemlidy in children younger than 12 years of age, or weighing < 35 kg, have not yet been established. No data are available.

Method of administration

Oral administration. Vemlidy film-coated tablets should be taken with food.

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

HBV transmission

Patients must be advised that Vemlidy does not prevent the risk of transmission of HBV to others through sexual contact or contamination with blood. Appropriate precautions must continue to be used.

Patients with decompensated liver disease

There are no data on the safety and efficacy of Vemlidy in HBV-infected patients with decompensated liver disease and who have a Child Pugh Turcotte (CPT) score > 9 (i.e. class C). These patients may be at higher risk of experiencing serious hepatic or renal adverse reactions. Therefore, hepatobiliary and renal parameters should be closely monitored in this patient population (see section 5.2).

Exacerbation of hepatitis

Flares on treatment

Spontaneous exacerbations in chronic hepatitis B are relatively common and are characterised by transient increases in serum alanine aminotransferase (ALT). After initiating antiviral therapy, serum ALT may increase in some patients. In patients with compensated liver disease, these increases in serum ALT are generally not accompanied by an increase in serum bilirubin concentrations or hepatic decompensation. Patients with cirrhosis may be at a higher risk for hepatic decompensation following hepatitis exacerbation, and therefore should be monitored closely during therapy.

Flares after treatment discontinuation

Acute exacerbation of hepatitis has been reported in patients who have discontinued treatment for hepatitis B, usually in association with rising HBV DNA levels in plasma. The majority of cases are self-limited but severe exacerbations, including fatal outcomes, may occur after discontinuation of treatment for hepatitis B. Hepatic function should be monitored at repeated intervals with both clinical and laboratory follow-up for at least 6 months after discontinuation of treatment for hepatitis B. If appropriate, resumption of hepatitis B therapy may be warranted.

In patients with advanced liver disease or cirrhosis, treatment discontinuation is not recommended since post-treatment exacerbation of hepatitis may lead to hepatic decompensation. Liver flares are especially serious, and sometimes fatal in patients with decompensated liver disease.

Renal impairment

Patients with creatinine clearance < 30 mL/min

The use of Vemlidy once daily in patients with CrCl ≥ 15 mL/min but < 30 mL/min and in patients with CrCl < 15 mL/min who are receiving haemodialysis is based on very limited pharmacokinetic data and on modelling and simulation. There are no safety data on the use of Vemlidy to treat HBV-infected patients with CrCl < 30 mL/min.

The use of Vemlidy is not recommended in patients with CrCl < 15 mL/min who are not receiving haemodialysis (see section 4.2).

Nephrotoxicity

A potential risk of nephrotoxicity resulting from chronic exposure to low levels of tenofovir due to dosing with tenofovir alafenamide cannot be excluded (see section 5.3).

Patients co-infected with HBV and hepatitis C or D virus

There are no data on the safety and efficacy of Vemlidy in patients co-infected with hepatitis C or D virus. Co-administration guidance for the treatment of hepatitis C should be followed (see section 4.5).

Hepatitis B and HIV co-infection

HIV antibody testing should be offered to all HBV-infected patients whose HIV-1 infection status is unknown before initiating therapy with Vemlidy. In patients who are co-infected with HBV and HIV, Vemlidy should be co-administered with other antiretroviral agents to ensure that the patient receives an appropriate regimen for treatment of HIV (see section 4.5).

Co-administration with other medicinal products

Vemlidy should not be co-administered with products containing tenofovir alafenamide, tenofovir disoproxil fumarate or adefovir dipivoxil.

Co-administration of Vemlidy with certain anticonvulsants (e.g. carbamazepine, oxcarbazepine, phenobarbital and phenytoin), antimycobacterials (e.g. rifampicin, rifabutin and rifapentine) or St. John's wort, all of which are inducers of P-glycoprotein (P-gp) and may decrease tenofovir alafenamide plasma concentrations, is not recommended.

Co-administration of Vemlidy with strong inhibitors of P-gp (e.g. itraconazole and ketoconazole) may increase tenofovir alafenamide plasma concentrations. Co-administration is not recommended.

Lactose intolerance

Vemlidy contains lactose monohydrate. Consequently, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.