Vemlidy

/ Gilead

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:
In HBeAg-positive patients without cirrhosis, treatment should be administered for at least 6-12 months after HBe sero-conversion (HBeAg loss and HBV DNA loss with anti-HBe detection) is confirmed or until HBs sero-conversion or until there is loss of efficacy. 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 this drug 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 this drug, the patient should take another tablet. If the patient vomits more than 1 hour after taking this drug, the patient does not need to take another tablet. See prescribing information for full details.
Elderly: No dose adjustment is required in patients aged 65 years and older.
Renal impairment: No dose adjustment of tenofovir 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, this drug should be administered after completion of haemodialysis treatment.
No dosing recommendations can be given for patients with CrCl < 15 mL/min who are not receiving haemodialysis.
Hepatic impairment: No dose adjustment of this drug is required in patients with hepatic impairment.
Paediatric population: The safety and efficacy of this drug 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. This drug film-coated tablets should be taken with food. There is no information available regarding the crushing/splitting of the product. It is recommended that the film-coated tablet is not chewed, split or crushed.
See prescribing information for full details.

Treatment of chronic hepatitis B in adults and adolescents (aged 12 years and older with body weight at least 35 kg).

Hypersensitivity to the active substance or to any of the excipients.

HBV transmission: Patients must be advised that this drug 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 this agent 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.
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 this drug 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 this drug to treat HBV-infected patients with CrCl < 30 mL/min.
The use of this drug is not recommended in patients with CrCl < 15 mL/min who are not receiving haemodialysis.
Nephrotoxicity: A potential risk of nephrotoxicity resulting from chronic exposure to low levels of tenofovir due to dosing with tenofovir alafenamide cannot be excluded. It is recommended that renal function is assessed in all patients prior to, or when initiating, therapy with Vemlidy 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 Vemlidy should be considered.
Patients co-infected with HBV and hepatitis C or D virus: There are no data on the safety and efficacy of this drug in patients co-infected with hepatitis C or D virus. Co-administration guidance for the treatment of hepatitis C should be followed.
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 this drug. In patients who are co-infected with HBV and HIV, The drug should be co-administered with other antiretroviral agents to ensure that the patient receives an appropriate regimen for treatment of HIV.
Co-administration with other medicinal products: Vemlidy should not be co-administered with products containing tenofovir alafenamide, tenofovir disoproxil 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. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Common: Diarrhea, vomiting, nausea, abdominal pain, abdominal distension, flatulence Fatigue Gastrointestinal disorders, headache, dizziness, rash, pruritus, hepatobiliary disorders, increased ALT, arthralgia.
See prescribing information for full details.

Interaction studies have only been performed in adults.
This drug should not be co-administered with medicinal products containing tenofovir disoproxil, tenofovir alafenamide or adefovir dipivoxil.
Medicinal products that may affect tenofovir alafenamide: Tenofovir alafenamide is transported by P-gp and breast cancer resistance protein (BCRP). Medicinal products that are P-gp inducers (e.g., rifampicin, rifabutin, carbamazepine, phenobarbital or St. John’s wort) are expected to decrease plasma concentrations of tenofovir alafenamide, which may lead to loss of therapeutic effect of Tenofovir alafenamide. Co-administration of such medicinal products is not recommended.
Co-administration with medicinal products that inhibit P-gp and BCRP may increase plasma concentration of tenofovir alafenamide. Co-administration of strong inhibitors of P-gp with this drug is not recommended.
Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and/or OATP1B3.
Effect of tenofovir alafenamide on other medicinal products: Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 in vitro. It is not an inhibitor or inducer of CYP3A in vivo.
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase (UGT) 1A1 in vitro. It is not known whether tenofovir alafenamide is an inhibitor of other UGT enzymes.
See prescribing information for full details.

Pregnancy: There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of tenofovir alafenamide in pregnant women. However, a large amount of data on pregnant women (more than 1000 exposed outcomes) indicates no malformative nor feto/neonatal toxicity associated with the use of tenofovir disoproxil. The use of tenofovir alafenamide may be considered during pregnancy, if necessary.
Lactation: It is not known whether tenofovir alafenamide is secreted in human milk. However, in animal studies it has been shown that tenofovir is secreted into milk. There is insufficient information on the effects of tenofovir in newborns/infants. A risk to the breastfed child cannot be excluded; therefore, tenofovir alafenamide should not be used during breast-feeding.
Fertility: No human data on the effect of tenofovir alafenamide on fertility are available. Animal studies do not indicate harmful effects of tenofovir alafenamide on fertility.

If overdose occurs the patient must be monitored for evidence of toxicity.
Treatment of overdose with this drug consists of general supportive measures including monitoring of vital signs as well as observation of the clinical status of the patient.
Tenofovir is efficiently removed by haemodialysis with an extraction coefficient of approximately 54%. It is not known whether tenofovir can be removed by peritoneal dialysis.

Shelf life: In use: 90 days after first opening.
Storage: Store below 30°C.