Coadministration with methadone (60-100 mg once daily, individualised dose) decreased the AUC, Cmin and Cmax of R-methadone by 16%, 225 and 14%, respectively. There were no changes in rilpivirine AUC, Cmin and Cmax when compared to historic controls.  No dose adjustments are required when initiating co-administration of methadone with rilpivirine. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and medicinal products that prolong the QTc interval of the ECG. In a study of healthy subjects, supratherapeutic doses of rilpivirine (75 mg once daily and 300 mg once daily) have been shown to prolong the QTc interval of the electrocardiogram (ECG). Rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Rilpivirine should be used with caution when co-administered with medicinal products with a known risk of Torsade de Pointes.

No dose adjustments are required when initiating co-administration of methadone with rilpivirine. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. When compared to historical controls, coadministration of rilpivirine (25 mg once daily) and methadone (60-100 mg once daily, individualised doses) to 12 subjects had no effect on rilpivirine Cmax, AUC and Cmin.  The Cmax, AUC and Cmin of R-methadone decreased by 14%, 16% and 22%, respectively, whilst those of S-methadone decreased by 13%, 16% and 21%, respectively. There is limited information available on the potential for a pharmacodynamic interaction between rilpivirine and drugs that prolong the QTc interval of the electrocardiogram. In healthy subjects, 75 mg once daily and 300 mg once daily (3 times and 12 times the dose in Edurant) have been shown to prolong the QTc interval of the electrocardiogram. Consider alternatives to rilpivirine when coadministered with a drug that is known to have a risk of torsade de pointes.

When compared to historical controls, coadministration of rilpivirine (25 mg once daily) and methadone (60-100 mg once daily, individualised doses) to 12 subjects had no effect on rilpivirine Cmax, AUC and Cmin.  The Cmax, AUC and Cmin of R-methadone decreased by 14%, 16% and 22%, respectively, whilst those of S-methadone decreased by 13%, 16% and 21%, respectively.