JULUCA

Juluca should be prescribed by physicians experienced in the management of HIV infection. Posology The recommended dose of Juluca is one tablet once daily. 2). 5). In these cases, the physician should refer to the Summary of Product Characteristics for these medicinal products.

Missed doses If the patient misses a dose of Juluca, the patient should take Juluca with a meal as soon as possible, providing the next dose is not due within 12 hours. If the next dose is due within 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 Juluca, another Juluca tablet should be taken with a meal. If a patient vomits more than 4 hours after taking Juluca, the patient does not need to take another dose of Juluca until the next regularly scheduled dose.

Elderly There are limited data available on the use of Juluca in patients aged 65 years and over. 2). Renal impairment No dosage adjustment is required in patients with mild or moderate renal impairment. In patients with severe renal impairment or end stage renal disease, the combination of Juluca with a strong CYP3A inhibitor should only be used if the benefit outweighs the risk.

2). Hepatic impairment No dosage adjustment is required in patients with mild or moderate hepatic impairment (Child-Pugh score A or B). Juluca should be used with caution in patients with moderate hepatic impairment. 2). Paediatric population The safety and efficacy of Juluca in children and adolescents aged less than 18 years have not yet been established.

2, but no recommendation on a posology can be made. Pregnancy The safety and efficacy of Juluca in pregnancy have not yet been established. Limited data are available regarding the use of dolutegravir during pregnancy. Lower exposures of dolutegravir and rilpivirine were observed during pregnancy.

No recommendations for dose adjustments can be made for Juluca. 2). 2). It is recommended that the film-coated tablet be swallowed whole with water and not be chewed or crushed.

Summary of the safety profile Clinical safety data with Juluca is limited. 1), were diarrhoea (2%) and headache (2%). 4). Tabulated list of adverse reactions The adverse reactions considered at least possibly related to treatment with the components of Juluca from clinical studies and post-marketing experience are listed in Table 2 by body system, organ class and frequency.

Frequencies are defined as very common ( 1/10), common ( 1/100 to <1/10), uncommon ( 1/1,000 to <1/100), rare ( 1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data). 4)Immune system disorders not known immune reconstitution syndrome very common increased total cholesterol (fasted) increased LDL cholesterol (fasted) Metabolism and nutrition disorders common decreased appetite increased triglycerides (fasted) very common insomnia common abnormal dreams depression sleep disorders depressed mood anxiety Psychiatric disorders uncommon suicidal ideation or suicide attempt (particularly in patients with a pre-existing history of depression or psychiatric illness), panic attack rare completed suicide (particularly in patients with a pre-existing history of depression or psychiatric illness) very common headache dizziness Nervous system disorders common somnolence Gastrointestinal disorders very common nausea increased pancreatic amylase diarrhoea common abdominal pain vomiting flatulence increased lipase abdominal discomfort upper abdominal pain dry mouth very common increased transaminases (alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) elevations) common increased bilirubin uncommon hepatitis Hepatobiliary disorders rare acute hepatic failure3 Skin and subcutaneous tissue disorders common rash pruritus Musculoskeletal and connective tissue disorders uncommon arthralgia myalgia General disorders and administration site conditions common fatigue Investigations common creatine phosphokinase (CPK) elevations, weight increased 1 Frequencies are assigned based on the maximum frequencies observed in the pooled SWORD studies or studies with the individual components 2 Reversible sideroblastic anaemia has been reported in dolutegravir-containing regimens.

The contribution of dolutegravir in these cases is unclear. 3 This adverse reaction was identified through post-marketing surveillance for dolutegravir in combination with other ARVs. The frequency category of rare was estimated based on post-marketing reports.

Description of selected adverse reactions Changes in laboratory biochemistries Dolutegravir or rilpivirine have been associated with increases in serum creatinine occurring in the first week of treatment when administered with other antiretroviral medicinal products.

Increases in serum creatinine occurred within the first four weeks of treatment with Juluca and remained stable through 148 weeks. 4 mol/L) was observed after 148 weeks treatment. These changes are related to inhibition of active transport, and are not considered to be clinically relevant as they do not reflect a change in glomerular filtration rate.

4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Hypersensitivity reactions Hypersensitivity reactions have been reported with dolutegravir, and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including severe liver reactions. Juluca should be discontinued immediately if signs or symptoms of hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by raised liver enzymes, fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial oedema, eosinophilia, angioedema).

Clinical status including liver aminotransferases and bilirubin should be monitored. Delay in stopping treatment with Juluca after the onset of hypersensitivity may result in a life-threatening allergic reaction. 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 lifestyle. For lipids and weight, there is in some cases evidence for a treatment effect. For monitoring of blood lipids and glucose reference is made to established HIV treatment guidelines.

Lipid disorders should be managed as clinically appropriate. 1). Rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Juluca should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.

Opportunistic infections Patients should be advised that Juluca does not cure HIV infection and that they may still develop opportunistic infections and other complications of HIV infection. Therefore, patients should remain under close clinical observation by physicians experienced in the treatment of these associated HIV diseases.

Osteonecrosis Although the aetiology is considered to be multifactorial (including corticosteroid use, biphosphonates, alcohol consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been reported 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. Patients with hepatitis B or C No clinical data are available in patients with hepatitis B co-infection.

Physicians should refer to current treatment guidelines for the management of HIV infection in patients co-infected with hepatitis B virus. Limited data is available in patients with hepatitis C co-infection. A higher incidence of liver chemistry elevations (Grade 1) were observed in patients treated with dolutegravir and rilpivirine co-infected with hepatitis C compared to those who were not co-infected.

Monitoring of liver function is recommended in patients with hepatitis B and/or C co-infection. 5). Juluca should not be co-administered at the same time as H2-receptor antagonists. 5). Juluca should not be co-administered at the same time as antacids.

5). Calcium or iron supplements, or multivitamins should be co-administered at the same time as Juluca, with a meal. 5). Dolutegravir increased metformin concentrations. 5). Metformin is eliminated renally and therefore, it is of importance to monitor renal function when co-treated with Juluca.

This combination may increase the risk for lactic acidosis in patients with moderate renal impairment (stage 3a creatinine clearance [CrCl] 45– 59 mL/min) and a cautious approach is recommended. Reduction of the metformin dose should be highly considered.

5). Pregnancy The safety and efficacy of Juluca in pregnancy have not yet been established. Limited data are available regarding the use of dolutegravir during pregnancy. Lower exposures of dolutegravir or rilpivirine were observed when taken once daily, in combination with a background regimen, during pregnancy.

In phase 3 studies, lower rilpivirine exposure, similar to that seen during pregnancy, has been associated with an increased risk of virological failure. No recommendations for dose adjustments can be made for Juluca. 2). Immune Reactivation Syndrome In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy (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 evaluated and treatment instituted when necessary. Autoimmune disorders (such as Graves’ disease and autoimmune […]

1. Co-administration with the following medicinal products: - fampridine (also known as dalfampridine); - carbamazepine, oxcarbazepine, phenobarbital, phenytoin; - rifampicin, rifapentine; - proton pump inhibitors, such as omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole; - systemic dexamethasone, except as a single dose treatment; - St John's wort (Hypericum perforatum).