Emtricitabine/tenofovir-DF should not be administered with additional tenofovir-DF. Coadministration of tenofovir-DF (300 mg once daily) and emtricitabine (200 mg once daily for 7 days) had no effect on tenofovir AUC, Cmax or Cmin; emtricitabine AUC and Cmax were unaltered and there was a 20% increase in Cmin (n=17).

Coadministration of clopidogrel and boosted regimens has been evaluated in clinical studies. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. In HIV-positive subjects, the presence of a pharmacoenhancer (ritonavir n=8; cobicistat n=1) decreased the AUC and Cmax of clopidogrel’s active metabolite both by 69% when compared to values obtained in HIV-negative subjects (n=12). In HIV-negative subjects (n=12), coadministration of clopidogrel and ritonavir (100 mg twice daily) decreased the AUC and Cmax of clopidogrel’s active metabolite by 51% and 48%. Importantly, the decrease in clopidogrel’s active metabolite lead to insufficient inhibition of platelet aggregation in 44% of the patients treated with clopidogrel and ritonavir or cobicistat. Consistently, the study in HIV-negative subjects showed that the average inhibition of platelet aggregation was decreased from 51% (clopidogrel alone) to 31% (clopidogrel + ritonavir). Of interest, the study with HIV-infected patients showed a comparable decrease in prasugrel’s active metabolite AUC (52% decrease), however this decrease did not impair prasugrel’s antiplatelet effect. The differential impact on clopidogrel and prasugrel pharmacodynamics effect is in line with clinical observations. Early thrombosis of a coronary stent was reported in a patient treated with darunavir/ritonavir concomitantly with clopidogrel while subsequent replacement of clopidogrel by prasugrel did not lead to novel stent thrombosis episodes. Taken together these data suggest that given the risk of diminished clopidogrel response, prasugrel should be preferred in presence of boosted regimens, unless the patient has a clinical condition which contraindicates its use in which case an alternative antiplatelet agent should be considered.

Coadministration is contraindicated due to the potential for serious reactions such as myopathy including rhabdomyolysis. Simvastatin is metabolised by CYP3A4 and coadministration may increase concentrations.

Descovy contains tenofovir alafenamide and therefore should not be administered with tenofovir-DF.

Emtricitabine/tenofovir-DF should not be administered with additional emtricitabine or with tenofovir alafenamide.

Coadministration with emtricitabine/tenofovir-DF has not been studied. Coadministration of tenofovir-DF (300 mg once daily) and atazanavir/ritonavir (300/100 mg once daily) was studied in 12 subjects. Atazanavir AUC, Cmax and Cmin decreased by 25%, 28% and 26%, respectively. Tenofovir AUC, Cmax and Cmin increased by 37%, 34% and 29%, respectively. No dose adjustment is recommended. The increased exposure of tenofovir could potentiate tenofovir associated adverse events, including renal disorders. Renal function should be closely monitored. In HIV-1 infected patients with renal risk factors, the co-administration of tenofovir-DF with a boosted protease inhibitor should be carefully evaluated. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Atazanavir/cobicistat should not be coadministered with emtricitabine or tenofovir-DF in patients with creatinine clearance less than 70 ml/min.

Coadministration has not been studied. The combination of tenofovir-DF (300 mg) and atazanavir (400 mg) reduced atazanavir AUC, Cmax and Cmin decreased by 25%, 21% and 40%, respectively, but increased tenofovir AUC, Cmax and Cmin by 24%, 14% and 22%, respectively. Atazanavir/cobicistat is also expected to increase tenofovir plasma concentrations. Patients should be closely monitored for tenofovir-associated adverse events, including renal disorders. The European SmPC recommends that atazanavir/cobicistat and tenofovir be given together with food. Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Atazanavir/cobicistat should not be coadministered with emtricitabine in patients with creatinine clearance less than 70 ml/min.

Coadministration has not been studied. Buspirone is metabolized by CYP3A4 but does not inhibit CYP3A4. Atazanavir/cobicistat could potentially increase buspirone concentrations. A low dose of buspirone used cautiously is recommended and adjust dosage based on the clinical response.

Coadministration has not been studied. Metoprolol is mainly metabolized by CYP2D6. Atazanavir/cobicistat could potentially increase metoprolol concentrations although to a moderate extent as cobicistat is a weak inhibitor of CYP2D6. Pharmacokinetic studies between atazanavir and drugs that prolong the PR interval including beta blockers (other than atenolol) have not been performed. An additive effect of atazanavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those receiving known atrioventricular nodal blocking agents. The atazanavir/cobicistat SmPC recommends clinical monitoring. A dose reduction of metoprolol may be necessary.

Coadministration of atazanavir/cobicistat (300/150 mg once daily) and atorvastatin (10 mg) increased atorvastatin AUC and Cmax by 822% and 1785% due to inhibition of CYP3A, OATP1B1 and BCRP by atazanavir/cobicistat. There was no effect of atorvastatin on atazanavir/cobicistat exposure. Coadministration is not recommended. If the use of atorvastatin is considered strictly necessary, the lowest possible dose of atorvastatin should be used and the daily dose should not exceed 10 mg with careful monitoring.

Coadministration with emtricitabine/TAF has not been studied. Coadministration of atazanavir/cobicistat (300/150 mg once daily) and tenofovir alafenamide increased tenofovir alafenamide AUC and Cmax by 75% and 80%. No significant effects were observed on atazanavir pharmacokinetics. When administered with atazanavir/cobicistat, the recommended dose of emtricitabine/tenofovir alafenamide is 200/10 mg once daily (where available). Cobicistat has been shown to decrease estimated creatinine clearance due to inhibition of tubular secretion of creatinine without affecting actual renal glomerular function. Atazanavir/cobicistat should not be coadministered with emtricitabine in patients with creatinine clearance less than 70 ml/min.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as buspirone is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atorvastatin is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral.

Coadministration has not been studied but based on the metabolism and clearance a clinically significant interaction is unlikely. Buspirone is metabolized by CYP3A4. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Metoprolol is mainly metabolized by CYP2D6. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atorvastatin is metabolized by CYP3A4. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Simvastatin is metabolized by CYP3A4. Emtricitabine and tenofovir alafenamide do not interact with this metabolic pathway. Dose Descovy according to the concomitant antiretroviral.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clopidogrel is a prodrug that is converted to its active metabolites via CYPs 3A4, 2B6, 2C19 and 1A2.