EMTRICITABINE/RILPIVIRINE/TENOFOVIR DISOPROXIL GILEAD

Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead should be initiated by a physician experienced in the management of HIV infection. Posology Adults The recommended dose of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is one tablet, taken orally, once daily.

2). Where discontinuation of therapy with one of the components of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is indicated or where dose modification is necessary, separate preparations of emtricitabine, rilpivirine hydrochloride and tenofovir disoproxil are available.

Please refer to the Summary of Product Characteristics for these medicinal products. If a patient misses a dose of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead within 12 hours of the time it is usually taken, the patient should take Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead with food as soon as possible and resume the normal dosing schedule.

If a patient misses a dose of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead by more than 12 hours, the patient should not take the missed dose and simply resume the usual dosing schedule. If a patient vomits within 4 hours of taking Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead another Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead tablet should be taken with food.

If a patient vomits more than 4 hours after taking Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead they do not need to take another dose of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead until the next regularly scheduled dose.

5). Special populations Elderly Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead has not been studied in patients over the age of 65 years. 2). 8). Limited data from clinical studies support once daily dosing of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead in patients with mild renal impairment (creatinine clearance (CrCl) 50-80 mL/min).

However, long-term safety data for the emtricitabine and tenofovir disoproxil components of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead have not been evaluated in patients with mild renal impairment. 2). Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is not recommended for patients with moderate or severe renal impairment (CrCl < 50 mL/min).

2). Hepatic impairment There is limited information regarding the use of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead in patients with mild or moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Score A or B). No dose adjustment of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is required in patients with mild or moderate hepatic impairment.

Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead should be used with caution in patients with moderate hepatic impairment. Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead has not been studied in patients with severe hepatic impairment (CPT Score C).

2). 4). Paediatric population The safety and efficacy of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead in children under the age of 18 years have not been established. 2, but no recommendation on a posology can be made. Pregnancy Lower exposures of rilpivirine (one of the components of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead) were observed during pregnancy; therefore viral load should be monitored closely.

2). 2). It is recommended that Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead be swallowed whole with water. The film-coated tablet should not be chewed, crushed or split as it may impact the absorption of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead.

Summary of the safety profile The combination of emtricitabine, rilpivirine and tenofovir disoproxil has been studied as the component products in treatment-naïve patients (Phase III studies C209 and C215). The single-tablet regimen (STR), Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead, has been studied in virologically suppressed patients who switched from a regimen containing a ritonavir-boosted PI (Phase III study GS-US-264-0106) or from efavirenz/emtricitabine/tenofovir disoproxil (Phase IIb study GS-US-264-0111).

1). In virologically suppressed patients switching to Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead, the most frequently reported adverse reactions considered possibly or probably related to Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead were fatigue (3%), diarrhoea (3%), nausea (2%) and insomnia (2%) (48 week data from the Phase III study GS-US-264-0106).

The safety profile of emtricitabine and tenofovir disoproxil in these studies was consistent with the previous experience with these agents when each was administered with other antiretroviral agents. In patients receiving tenofovir disoproxil, rare events of renal impairment, renal failure and uncommon events of proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities (infrequently contributing to fractures) have been reported.

4). 4). Tabulated summary of adverse reactions The adverse reactions considered at least possibly related to treatment with the components of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead from clinical study and post-marketing experience are listed in Table 2, below, by body system organ class and frequency.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100) or rare (≥ 1/10,000 to < 1/1,000).

Table 2:

Tabulated summary of adverse reactions to Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead based on clinical study and post-marketing experience with Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead and its individual components Frequency Adverse reaction Blood and lymphatic system disorders Common: neutropenia1, decreased white blood cell count2, decreased haemoglobin2, decreased platelet count2 Uncommon: anaemia1, 4 Immune system disorders Common: allergic reaction1 Uncommon: immune reactivation syndrome Metabolism and nutrition disorders Very common: increased total cholesterol (fasted)2, increased LDL-cholesterol (fasted)2, hypophosphataemia3, 5 Common: hypertriglyceridaemia1, 2, hyperglycaemia1, decreased appetite2 Uncommon: hypokalaemia3, 5 Rare: lactic acidosis3 Psychiatric disorders Very common: insomnia1, 2 Common: depression2, depressed mood2, sleep disorders2, abnormal dreams1, 2 Nervous system disorders Very common: headache1, 2, 3, dizziness1, 2, 3 Common: somnolence2 Gastrointestinal disorders Very common: increased pancreatic amylase2, vomiting1, 2, 3, diarrhoea1, 3, nausea1, 2, 3 Common: elevated amylase including elevated pancreatic amylase1, elevated serum lipase1, 2, abdominal pain1, 2, 3, abdominal discomfort2, abdominal distension3, dyspepsia1, flatulence3, dry mouth2 Uncommon: pancreatitis3 Hepatobiliary disorders Very common: increased transaminases (AST and/or ALT)1, 2, 3 Common: increased bilirubin1, 2 Rare: hepatitis3, hepatic steatosis3 Frequency Adverse reaction Skin and subcutaneous tissue disorders Very common: rash1, 2, 3 Common: vesiculobullous rash1, pustular rash1, urticaria1, skin discolouration (increased pigmentation)1, 4, maculopapular rash1, pruritus1 Uncommon: angioedema1, 3, 6, severe skin reactions with systemic symptoms7 Musculoskeletal and connective tissue disorders Very common: elevated creatine kinase1 Common: bone mineral density decreased3 Uncommon: rhabdomyolysis3, 5, muscular weakness3, 5 Rare: osteomalacia (manifested as bone pain and infrequently contributing to fractures)3, 5, 8, myopathy3, 5 Renal and urinary disorders Uncommon: proximal renal tubulopathy including Fanconi syndrome3, increased creatinine3, proteinuria3 Rare: renal failure (acute and chronic)3, acute tubular necrosis3, nephritis (including acute interstitial nephritis)3, 8, nephrogenic diabetes insipidus3 General disorders and administration site conditions Very common: asthenia1, 3 Common: pain1, fatigue2 1 Adverse reaction identified for emtricitabine.

2 Adverse reaction identified for rilpivirine hydrochloride. 3 Adverse reaction identified for tenofovir disoproxil. 8, Paediatric population). 5 This adverse reaction may occur as a consequence of proximal renal tubulopathy. It is not considered to be causally associated with tenofovir disoproxil in the absence of this condition.

6 This was a rare adverse reaction for tenofovir disoproxil. It was also identified as an adverse reaction for emtricitabine through post-marketing surveillance but was not observed in randomised controlled clinical studies in adults or paediatric HIV clinical studies of emtricitabine.

The frequency category of uncommon was […]

Virologic failure and development of resistance Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead has not been evaluated in patients with previous virologic failure to any other antiretroviral therapy. There is not sufficient data to justify the use in patients with prior NNRTI failure.

1). 4% with efavirenz). 1% in the emtricitabine/tenofovir disoproxil + efavirenz arm. The difference in the rate of new virologic failures from the week 48 to week 96 analysis between rilpivirine and efavirenz arms was not statistically significant.

Patients with a baseline viral load > 100,000 HIV-1 RNA copies/mL who experienced virologic failure exhibited a higher rate of treatment-emergent resistance to the NNRTI class. 1). 1). Rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc.

Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes. 5). 5). 5). 5). Renal impairment Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is not recommended for patients with moderate or severe renal impairment (CrCl < 50 mL/min).

2). 5). 8). Cases of acute renal failure after initiation of high dose or multiple non-steroidal anti-inflammatory drugs (NSAIDs) have been reported in patients treated with tenofovir disoproxil and with risk factors for renal dysfunction.

If Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is co-administered with an NSAID, renal function should be monitored adequately. 8). It is recommended that CrCl is calculated in all patients prior to initiating therapy with Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead and renal function (CrCl and serum phosphate) is also monitored after two to four weeks of treatment, after three months of treatment and every three to six months thereafter in patients without renal risk factors.

In patients at risk for renal impairment, a more frequent monitoring of renal function is required. 8, proximal tubulopathy). 32 mmol/L). Interrupting treatment with Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead should also be considered in case of progressive decline of renal function when no other cause has been identified.

Where discontinuation of therapy with one of the components of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead is indicated or where dose modification is necessary, separate preparations of emtricitabine, rilpivirine hydrochloride and tenofovir disoproxil are available.

Bone effects A dual energy X ray absorptiometry (DXA) substudy for both the Phase III studies (C209 and C215) […]

1. Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead should not be co-administered with the following medicinal products as significant decreases in rilpivirine plasma concentrations may occur (due to cytochrome P450 [CYP]3A enzyme induction or gastric pH increase), which may result in loss of therapeutic effect of Emtricitabine/Rilpivirine/Tenofovir Disoproxil Gilead: • the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin • the antimycobacterials rifampicin, rifapentine • proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole • the systemic glucocorticoid dexamethasone, except as a single dose treatment • St.

John’s wort (Hypericum perforatum)