Coadministration of oral rilpivirine and methadone (60-100 mg once daily individualised dose) decreased R-methadone AUC, Cmin and Cmax by 16%, 22% and 14%, respectively. There was no change in rilpivirine AUC, Cmin or Cmax based on historical 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. Rekambys should be used with caution when co-administered with a medicinal product with a known risk of Torsade de Pointes. At supra-therapeutic doses (75 and 300 mg once daily), oral rilpivirine has been associated with prolongation of the QTc interval of the electrocardiogram (ECG). Oral rilpivirine at the recommended dose of 25 mg once daily is not associated with a clinically relevant effect on QTc. Plasma rilpivirine concentrations after Rekambys injections are comparable to those during such oral rilpivirine therapy.

Coadministration is not expected to affect cabotegravir and had no effect on rilpivirine, but coadministration decreased methadone concentrations. Coadministration of methadone (60-100 mg once daily, individualized dose) and oral rilpivirine (25 mg once daily) was studied in 12 subjects. There was no effect on rilpivirine Cmax, AUC or Cmin when compared to historic controls. Data from 13 subjects showed R-methadone Cmax, AUC and Cmin decreased by 14%, 16% and 22%; S-methadone Cmax, AUC and Cmin decreased by 13%, 16% and 21%. No dose adjustment of methadone is required when starting coadministration of methadone with Cabenuva. However, clinical monitoring is recommended as methadone maintenance therapy may need to be adjusted in some patients. At mean steady-state Cmax values 4.4-fold and 11.6-fold higher than those with the recommended 600-mg dose of rilpivirine extended-release injectable suspension, rilpivirine may prolong the QTc interval. Cabenuva should be used with caution in combination with drugs with a known risk of Torsade de Pointes.