Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hepatitis B Virus (HBV) transmission

Patients must be advised that this medicinal product 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 limited data on the safety and efficacy of tenofovir alafenamide 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 CHB 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 CHB, 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 CHB. 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 CHB. If appropriate, resumption of CHB 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 tenofovir alafenamide once daily in patients with CrCl ≥ 15 mL/min and < 30 mL/min is based on Week 96 data on the efficacy and safety of switching from another antiviral regimen to tenofovir alafenamide in an open-label clinical study of virologically suppressed HBV infected patients (see sections 4.8 and 5.1). There are very limited data on the safety and efficacy of tenofovir alafenamide in HBV infected patients with CrCl < 15 mL/min on chronic haemodialysis (see sections 4.8, 5.1 and 5.2).

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

Nephrotoxicity

Post-marketing cases of renal impairment, including acute renal failure and proximal renal tubulopathy have been reported with tenofovir alafenamide-containing products. 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).

It is recommended that renal function is assessed in all patients prior to, or when initiating, therapy with this treatment and that it is also monitored during therapy in all patients as clinically appropriate.
In patients who develop clinically significant decreases in renal function, or evidence of proximal renal tubulopathy, discontinuation of this medicinal product should be considered.

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

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

HBV and Human Immunodeficiency Virus (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 this medicinal product. In patients who are co-infected with HBV and HIV, Vemlidy should be co-administered with other antiretroviral medicinal products to ensure that the patient receives an appropriate regimen for treatment of HIV (see section 4.5).

Co-administration with other medicinal products

This medicinal product should not be co-administered with medicinal products containing tenofovir alafenamide, tenofovir disoproxil or adefovir dipivoxil.

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

Excipients with known effect

This medicinal product contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Effects on Driving

4.7    Effects on ability to drive and use machines

Vemlidy may have minor influence on the ability to drive and use machines. Patients should be informed that dizziness has been reported during treatment with tenofovir alafenamide.