fection. 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.
Interactions with other medicinal products
Juluca should not be administered with other antiretroviral medicinal products for the treatment of HIV (see section 4.5).
Juluca should not be co-administered at the same time as H2-receptor antagonists. These medicinal products are recommended to be administered 12 hours before or 4 hours after Juluca (see section 4.5).
Juluca should not be co-administered at the same time as antacids. These medicinal products are recommended to be administered 6 hours before or 4 hours after Juluca (see section 4.5).
Calcium or iron supplements, or multivitamins should be co-administered at the same time as Juluca, with a meal. If calcium or iron supplements, or multivitamins cannot be taken at the same time as Juluca, these supplements are recommended to be administered 6 hours before or 4 hours after taking Juluca (see section 4.5).
Dolutegravir increased metformin concentrations. A dose adjustment of metformin should be considered when starting and stopping co-administration of Juluca with metformin, to maintain glycaemic control (see section 4.5). 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.
Juluca should not be taken with any other medicinal product containing dolutegravir or rilpivirine, except in case of co-administration with rifabutin (see section 4.5).
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. Therefore, use of Juluca during pregnancy is not recommended (see sections 4.6, 5.1 and 5.2).
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 eva luated and treatment instituted when necessary. Autoimmune disorders (such as Graves' disease |
