Vitekta 150 mg film-coated tablets

Each film-coated tablet contains 150 mg of elvitegravir.

Excipient with known effect: Each tablet contains 10.9 mg lactose (as monohydrate).

For the full list of excipients, see section 6.1.

Film-coated tablet (tablet).

Green, triangle-shaped, film-coated tablet of dimensions 10.9 mm x 10.5 mm, debossed with “GSI” on one side of the tablet and “150” on the other side of the tablet.

Vitekta co-administered with a ritonavir-boosted protease inhibitor and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus-1 (HIV-1) infection in adults who are infected with HIV-1 without known mutations associated with resistance to elvitegravir (see sections 4.2 and 5.1).

Therapy should be initiated by a physician experienced in the management of HIV infection.

Posology

Vitekta must be administered in combination with a ritonavir-boosted protease inhibitor.

The Summary of Product Characteristics for the co-administered ritonavir-boosted protease inhibitor should be consulted.

The recommended dose of Vitekta is one 85 mg tablet or one 150 mg tablet taken orally once daily with food. The choice of dose of Vitekta depends on the co-administered protease inhibitor (see Table 1 and sections 4.4 and 4.5). For use of the 85 mg tablet, please refer to the Summary of Product Characteristics for Vitekta 85 mg tablets.

Vitekta should be administered once daily as follows:

- Either at the same time as a once daily ritonavir-boosted protease inhibitor

- Or with the first dose of a twice daily ritonavir-boosted protease inhibitor.

Table 1: Recommended dosing regimens

There are no data to recommend the use of Vitekta with dosing frequencies or HIV-1 protease inhibitors other than those presented in Table 1.

Missed dose

If the patient misses a dose of Vitekta within 18 hours of the time it is usually taken, the patient should take Vitekta with food as soon as possible and resume the normal dosing schedule. If a patient misses a dose of Vitekta by more than 18 hours, and it is almost time for their next dose, the patient should not take the missed dose and simply resume the usual dosing schedule.

If the patient vomits within 1 hour of taking Vitekta another tablet should be taken.

Special populations

Elderly

No data are available on which to make a dose recommendation for patients over the age of 65 years (see section 5.2).

Renal impairment

No dose adjustment of Vitekta is required for patients with renal impairment (see section 5.2).

Hepatic impairment

No dose adjustment of Vitekta is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment (Child-Pugh Class B). Elvitegravir has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) (see sections 4.4 and 5.2).

Paediatric population

The safety and efficacy of elvitegravir in children aged 0 to less than 18 years have not yet been established (see section 5.1). No data are available.

Method of administration

Vitekta should be taken orally, once daily with food (see section 5.2). The film-coated tablet should not be chewed or crushed.

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

Co-administration with the following medicinal products due to the potential for loss of virologic response and possible development of resistance (see section 4.5):

• anticonvulsants: carbamazepine, phenobarbital, phenytoin

• antimycobacterials: rifampicin

• herbal products: St. John's wort (Hypericum perforatum)

General

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines.

The use of Vitekta with HIV-1 protease inhibitors or dosing frequencies other than those presented in Table 1 may result in inadequate or elevated plasma levels of elvitegravir and/or the co-administered medicinal products.

Resistance

Elvitegravir-resistant viruses show cross-resistance to the integrase strand transfer inhibitor raltegravir in most cases (see section 5.1).

Elvitegravir has a relatively low genetic barrier to resistance. Therefore, whenever possible, Vitekta should be administered with a fully active ritonavir-boosted protease inhibitor and a second fully active antiretroviral agent to minimise the potential for virologic failure and the development of resistance (see section 5.1).

Co-administration of other medicinal products

Elvitegravir is primarily metabolised by CYP3A. Co-administration of Vitekta with strong CYP3A inducers (including St. John's wort [Hypericum perforatum], rifampicin, carbamazepine, phenobarbital and phenytoin) is contraindicated (see sections 4.3 and 4.5). Co-administration of Vitekta with moderate CYP3A inducers (including, but not limited to, efavirenz and bosentan) is not recommended (see section 4.5).

Due to the need for co-administration of Vitekta with a ritonavir-boosted protease inhibitor, prescribers should consult the Summary of Product Characteristics of the co-administered protease inhibitor and ritonavir for a description of contraindicated medicinal products and other significant drug-drug interactions that may cause potentially life-threatening adverse reactions or loss of therapeutic effect and possible development of resistance.

Atazanavir/ritonavir and lopinavir/ritonavir have been shown to significantly increase the plasma concentrations of elvitegravir (see section 4.5). When used in combination with atazanavir/ritonavir and lopinavir/ritonavir, the dose of Vitekta should be decreased from 150 mg once daily to 85 mg once daily (see section 4.2). Please refer to the Summary of Product Characteristics for Vitekta 85 mg tablets.

Co-administration of Vitekta and related active substances: Vitekta must be used in combination with a ritonavir-boosted protease inhibitor. Vitekta should not be used with a protease inhibitor boosted by another agent as dosing recommendations for such combinations have not been established. Boosting elvitegravir with an agent other than ritonavir may result in suboptimal plasma concentrations of elvitegravir and/or the protease inhibitor leading to loss of therapeutic effect and possible development of resistance.

Vitekta should not be used in combination with products containing elvitegravir or pharmacokinetic boosting agents other than ritonavir.

Contraception requirements

Female patients of childbearing potential should use either a hormonal contraceptive containing at least 30 µg ethinylestradiol and containing norgestimate as the progestagen or should use an alternative reliable method of contraception (see sections 4.5 and 4.6). Co-administration of elvitegravir with oral contraceptives containing progestagens other than norgestimate have not been studied and, therefore, should be avoided.

Patients using oestrogens as hormone replacement therapy should be clinically monitored for signs of oestrogen deficiency (see section 4.5).

Opportunistic infections

Patients receiving Vitekta or any other antiretroviral therapy may continue to develop opportunistic infections and other complications of HIV infection, and therefore should remain under close clinical observation by physicians experienced in the treatment of patients with HIV associated diseases.

Patients with HIV and hepatitis B or C virus co-infection

Patients with chronic hepatitis B or C treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.

Physicians should refer to current HIV treatment guidelines for the optimal management of HIV infection in patients co-infected with hepatitis B virus (HBV).

Liver disease

Elvitegravir has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). No dose adjustment of Vitekta is required in patients with mild (Child-Pugh Class A) or moderate hepatic impairment (Child-Pugh Class B) (see sections 4.2 and 5.2).

Patients with pre-existing liver dysfunction, including chronic active hepatitis, have an increased frequency of liver function abnormalities during combination antiretroviral therapy (CART) and should be monitored according to standard practice. If there is evidence of worsening liver disease in such patients, interruption or discontinuation of treatment must be considered.

Weight and metabolic parameters

An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating this to any particular treatment. For monitoring of blood lipids and glucose reference is made to established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.

Immune Reactivation Syndrome

In HIV infected patients with severe immune deficiency at the time of institution of CART, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, such reactions have been observed within the first few weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be eva luated and treatment instituted when necessary.

Autoimmune disorders (such as Graves' disease) have also been reported to occur in the setting of immune reactivation; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.

Osteonecrosis

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported particularly in patients with advanced HIV disease and/or long-term exposure to CART. Patients should be advised to seek medical advice if they experience joint aches and pain, joint stiffness or difficulty in movement.

Excipients

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