As with other antiretroviral medicinal products, resistance testing should guide the use of rilpivirine.
Cardiovascular
At supra-therapeutic doses (75 and 300 mg once daily), rilpivirine has been associated with prolongation of the QTc interval of the electrocardiogram (ECG). Edurant at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Edurant should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.
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 pathogens may arise and cause serious clinical conditions or aggravation of symptoms. Typically, such reactions have been observed within the first weeks or months of initiation of CART. Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections and Pneumocystis jiroveci pneumonia. Any inflammatory symptoms should be evaluated and treatment instituted when necessary.
Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) 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.
Pregnancy
Edurant should be used during pregnancy only if the potential benefit justifies the potential risk. Lower exposures of rilpivirine were observed when rilpivirine 25 mg once daily was taken during pregnancy. In the Phase III studies, lower rilpivirine exposure, similar to that seen during pregnancy, has been associated with an increased risk of virological failure, therefore viral load should be monitored closely. Alternatively, switching to another ART regimen could be considered.
Important information about some of the ingredients of Edurant
Edurant contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Undesirable effects
During the clinical development program (1,368 patients in the Phase III controlled trials TMC278-C209 (ECHO) and TMC278-C215 (THRIVE)), 55.7% of subjects experienced at least one adverse drug reaction. The most frequently reported adverse drug reactions (ADRs) (>= 2%) that were at least of moderate intensity were depression (4.1%), headache (3.5%), insomnia (3.5%), rash (2.3%), and abdominal pain (2.0%). The most frequent serious treatment-related ADRs were reported in 7 (1.0%) patients receiving rilpivirine. The median duration of exposure for patients in the rilpivirine arm and efavirenz arm was 104.3 and 104.1 weeks, respectively. Most ADRs occurred in the first 48 weeks of treatment.
Selected treatment emergent clinical laboratory abnormalities (grade 3 or grade 4), considered as ADRs, reported in Edurant treated patients were increased pancreatic amylase (3.8%), increased AST (2.3%), increased ALT (1.6%), increased LDL cholesterol (fasted, 1.5%), decreased white blood cell count (1.2%), increased lipase (0.9%), increased bilirubin (0.7%), increased triglycerides (fasted, 0.6%), decreased haemoglobin (0.1%), decreased platelet count (0.1%), and increased total cholesterol (fasted, 0.1%).
Tabulated list of adverse reactions is available in the full information leaflet.
Description of selected adverse reactions
Immune reactivation syndrome
In HIV infected patients with severe immune deficiency at the time of initiation of combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic infections may arise. Autoimmune disorders (such as Graves' disease and autoimmune hepatitis) have also been reported; however, the reported time to onset is more variable and these events can occur many months after initiation of treatment.
Breast-feeding
It is not known whether rilpivirine is excreted in human milk. Rilpivirine is excreted in the milk of rats. Because of both the potential for HIV transmission and the potential for adverse reactions in breastfed infants, mothers should be instructed not to breast-feed if they are receiving rilpivirine.
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References
[1] Jaeger H et al. Week 96 efficacy and safety of cabotegravir + rilpivirine every 2 months: ATLAS-2M. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI) Virtual;
[2] Overton E et al. Long-acting cabotegravir and rilpivirine dosed every 2 months in adults with HIV-1 infection (ATLAS-2M), 48-week results: a randomised, multicentre, open-label, phase 3b, non-inferiority study.
[3] CABENUVA (cabotegravir, rilpivirine) Prescribing Information. US Approval
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