Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Virologic failure and development of resistance

EDURANT has not been evaluated in patients with previous virologic failure to any other antiretroviral therapy. The list of rilpivirine resistance-associated mutations presented in section 5.1 should only guide the use of EDURANT in the treatment-naïve population.

In the pooled efficacy analysis from the Phase III trials in adults through 96 weeks, patients treated with rilpivirine with a baseline viral load > 100,000 HIV-1 RNA copies/ml had a greater risk of virologic failure (18.2% with rilpivirine versus 7.9% with efavirenz) compared to patients with a baseline viral load ≤ 100,000 HIV-1 RNA copies/ml (5.7% with rilpivirine versus 3.6% with efavirenz). The greater risk of virologic failure for patients in the rilpivirine arm was observed in the first 48 weeks of these trials (see section 5.1). 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 non-nucleoside reverse transcriptase inhibitor (NNRTI) class.
More patients who failed virologically on rilpivirine than who failed virologically on efavirenz developed lamivudine/emtricitabine associated resistance (see section 5.1).

Findings in adolescents (12 to less than 18 years of age) in trial TMC278-C213 were generally in line with these data (for details see section 5.1).

As with other antiretroviral medicinal products, resistance testing should guide the use of rilpivirine (see section 5.1).

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) (see sections 4.5, 4.8 and 5.2).
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 (see section 4.8).

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 (see sections 4.6, 5.1 and 5.2). 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.

Effects on Driving

4.7     Effects on ability to drive and use machines

EDURANT has no or negligible influence on the ability to drive and use machines. However, fatigue, dizziness and somnolence have been reported in some patients taking EDURANT and should be considered when assessing a patient’s ability to drive or operate machinery.