EMTRICITABINE/TENOFOVIR ALAFENAMIDE GILEAD

Posology Treatment of HIV in adults and adolescents aged 12 years and older, weighing at least 35 kg: Therapy should be initiated by a physician experienced in the management of HIV infection. Emtricitabine/Tenofovir Alafenamide Gilead should be administered as shown in Table 1.

1. Pre-exposure prophylaxis of HIV in men who have sex with men (MSM), including adolescents (weighing at least 35 kg): One 200/25 mg tablet, once daily. Missed doses If a dose of Emtricitabine/Tenofovir Alafenamide Gilead is missed within 18 hours of the time it is usually taken, the individual should take Emtricitabine/Tenofovir Alafenamide Gilead as soon as possible and resume the normal dosing schedule.

If a dose of Emtricitabine/Tenofovir Alafenamide Gilead is missed by more than 18 hours, the individual should not take the missed dose and simply resume the usual dosing schedule. If the individual vomits within 1 hour of taking Emtricitabine/Tenofovir Alafenamide Gilead another tablet should be taken.

2). Renal impairment No dose adjustment of Emtricitabine/Tenofovir Alafenamide Gilead is required in adults or adolescents (aged at least 12 years and of at least 35 kg body weight) with estimated creatinine clearance (CrCl) ≥ 30 mL/min.

2). 2). On days of haemodialysis, Emtricitabine/Tenofovir Alafenamide Gilead should be administered after completion of haemodialysis treatment. Emtricitabine/Tenofovir Alafenamide Gilead should be avoided in individuals with estimated CrCl ≥ 15 mL/min and < 30 mL/min, or < 15 mL/min who are not on chronic haemodialysis, as the safety of Emtricitabine/Tenofovir Alafenamide Gilead has not been established in these populations.

No data are available to make dose recommendations in children less than 18 years with end stage renal disease. Hepatic impairment No dose adjustment of Emtricitabine/Tenofovir Alafenamide Gilead is required in individuals with hepatic impairment.

Paediatric population The safety and efficacy of Emtricitabine/Tenofovir Alafenamide Gilead in children younger than 12 years of age, or weighing < 35 kg, have not yet been established. No data are available. Women The efficacy of Emtricitabine/Tenofovir Alafenamide Gilead for PrEP in adult and adolescent women who have vaginal intercourse (or their partners) has not yet been established.

Method of administration Oral use. 2). It is recommended that the film-coated tablet is not chewed or crushed due to the bitter taste. For individuals who are unable to swallow the tablet whole, the tablet may be split in half and both halves taken one after the other, ensuring that the full dose is taken immediately.

Summary of the safety profile Treatment of HIV-1 infection:

Assessment of adverse reactions is based on safety data from across all Phase 2 and 3 studies in which HIV-1 infected patients received medicinal products containing emtricitabine and tenofovir alafenamide and from post- marketing experience.

In clinical studies of treatment-naïve adult patients receiving emtricitabine and tenofovir alafenamide with elvitegravir and cobicistat as the fixed- dose combination tablet elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide (as fumarate) 10 mg (E/C/F/TAF) through 144 weeks, the most frequently reported adverse reactions were diarrhoea (7%), nausea (11%), and headache (6%).

PrEP:

No new adverse reactions to Emtricitabine/Tenofovir Alafenamide Gilead were identified in the double-blind randomised placebo-controlled study (GS-US-412-2055) through 96 weeks in which 5,387 HIV-1 uninfected cisgender men and transgender women who have sex with men received Emtricitabine/Tenofovir Alafenamide Gilead or emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) once daily for HIV-1 PrEP.

The most common adverse reaction in participants who received Emtricitabine/Tenofovir Alafenamide Gilead was diarrhoea (5%) followed by nausea (4%), headache and fatigue (2%, respectively). Effects on biomarkers of renal and bone disease were similar to those observed in the treatment of HIV-1 with Emtricitabine/Tenofovir Alafenamide Gilead.

1). Tabulated summary of adverse reactions The adverse reactions in Table 3 are listed by system organ class and frequency. Frequencies are defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10) and uncommon (≥ 1/1,000 to < 1/100).

Table 3:

Tabulated list of adverse reactions1 Frequency Adverse reaction Blood and lymphatic system disorders Uncommon: anaemia2 Psychiatric disorders Common: abnormal dreams Nervous system disorders Common: headache, dizziness Gastrointestinal disorders Very common: nausea Common: diarrhoea, vomiting, abdominal pain, flatulence Uncommon: dyspepsia Skin and subcutaneous tissue disorders Common: rash Uncommon: angioedema3,4, pruritus, urticaria4 Musculoskeletal and connective tissue disorders Uncommon: arthralgia General disorders and administration site conditions Common: fatigue 1 With the exception of angioedema, anaemia and urticaria (see footnotes 2, 3 and 4), all adverse reactions were identified from clinical studies of F/TAF containing products.

The frequencies were derived from Phase 3 E/C/F/TAF clinical studies in 866 treatment-naïve adult patients through 144 weeks of treatment (GS-US-292-0104 and GS-US-292-0111). 2 This adverse reaction was not observed in the clinical studies of F/TAF-containing products but identified from clinical studies or post-marketing experience for emtricitabine when used with other antiretrovirals.

3 This adverse reaction was identified through post-marketing surveillance for emtricitabine-containing products. 4 This adverse reaction was identified through post-marketing surveillance for tenofovir alafenamide- containing products.

Description of selected adverse reactions Immune Reactivation Syndrome In HIV infected patients with severe immune deficiency at the time of initiation of CART, an inflammatory reaction to asymptomatic or residual opportunistic infections may arise.

4). Osteonecrosis Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk factors, advanced HIV disease or long-term exposure to CART. 4). Changes in lipid laboratory tests In studies in treatment- naïve patients, increases from baseline were observed in both the tenofovir alafenamide fumarate and tenofovir disoproxil fumarate containing treatment groups for the fasting lipid parameters total cholesterol, direct low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol, and triglycerides at Week 144.

001 for the difference between treatment groups for fasting total cholesterol, direct LDL- and HDL-cholesterol, and triglycerides). 006 for the difference between treatment groups). 009 for the difference between groups in changes from baseline).

There was little change from baseline in median fasting values for HDL cholesterol and glucose, or in the fasting total cholesterol to HDL cholesterol ratio in either treatment arm at Week 96. None of the changes was considered clinically relevant.

In a study of virologically suppressed adult patients switching from abacavir/lamivudine to Emtricitabine/Tenofovir Alafenamide Gilead while […]

Overall HIV-1 infection prevention strategy Emtricitabine/Tenofovir Alafenamide Gilead is not always effective in preventing the acquisition of HIV-1. The time to onset of protection after commencing Emtricitabine/Tenofovir Alafenamide Gilead is unknown.

Emtricitabine/Tenofovir Alafenamide Gilead for PrEP to reduce the risk of HIV-1 infection should be used as part of a comprehensive prevention strategy to reduce the risk of sexually acquired infection. , consistent and correct condom use, knowledge of partner HIV-1 status, regular testing for sexually transmitted infections that can facilitate HIV-1 transmission).

The efficacy of Emtricitabine/Tenofovir Alafenamide Gilead for PrEP in adult and adolescent women who have vaginal intercourse (or their partners) has not yet been established. 1). 3). g. at least every 3 months) using a combined antigen/antibody test while taking Emtricitabine/Tenofovir Alafenamide Gilead for PrEP.

Emtricitabine/Tenofovir Alafenamide Gilead alone does not constitute a complete regimen for the treatment of HIV-1, and HIV-1 resistance mutations have emerged in individuals with undetected HIV-1 infection who are only taking Emtricitabine/Tenofovir Alafenamide Gilead.

If clinical symptoms consistent with acute HIV-1 infection are present, and recent (<1 month) exposures to HIV-1 are suspected, follow local clinical guidelines and use an approved or cleared test to aid in the diagnosis of acute or primary HIV-1 infection.

1). HIV-1 uninfected individuals should be counselled at frequent intervals to strictly adhere to the recommended Emtricitabine/Tenofovir Alafenamide Gilead daily dosing schedule. Individuals co-infected with hepatitis B (HBV) or C (HCV) virus Individuals with chronic HBV or HCV treated with antiretroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions.

The safety and efficacy of Emtricitabine/Tenofovir Alafenamide Gilead in patients co-infected with HIV-1 and HCV have not been established. Discontinuation of Emtricitabine/Tenofovir Alafenamide Gilead in individuals infected with HBV may be associated with severe acute exacerbations of hepatitis.

Individuals infected with HBV who discontinue Emtricitabine/Tenofovir Alafenamide Gilead should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, initiation of anti-hepatitis B therapy may be warranted, especially in individuals with advanced liver disease or cirrhosis since post-treatment exacerbation of hepatitis may lead to hepatic decompensation.

The safety and efficacy of Emtricitabine/Tenofovir Alafenamide Gilead for PrEP in individuals with HBV or HCV infection have not been established. 2). Individuals 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 individuals, 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. Mitochondrial dysfunction following exposure in utero Nucleos(t)ide analogues may impact mitochondrial function to a variable degree, which is most pronounced with stavudine, didanosine and zidovudine.

There have been reports of mitochondrial dysfunction in HIV negative infants exposed in utero and/or postnatally to nucleoside analogues; these have predominantly concerned treatment with regimens containing zidovudine. The main adverse reactions reported are haematological disorders (anaemia, neutropenia) and metabolic disorders (hyperlactatemia, hyperlipasemia).

These events have often been transitory. Late onset neurological disorders have been reported rarely (hypertonia, convulsion, abnormal behaviour). Whether such neurological disorders are transient or permanent is currently unknown. These findings should be considered for any child exposed in utero to nucleos(t)ide analogues, who present with severe clinical findings of unknown aetiology, particularly neurologic findings.

These findings do not affect current national recommendations to use antiretroviral therapy in pregnant women to prevent vertical transmission of HIV. 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 […]

1. Use for PrEP in individuals with unknown HIV-1 status.