Kocitaf

Kocitaf Drug Interactions

Manufacturer:

Mylan

Distributor:

Atlanta Medicare
Full Prescribing Info
Drug Interactions
Interaction studies have only been performed in adults.
Dolutegravir, Emtricitabine and Tenofovir alafenamide should not be administered concomitantly with medicinal products containing tenofovir disoproxil (as fumarate), emtricitabine, lamivudine or adefovir dipivoxil.
Dolutegravir: Effect of other agents on the pharmacokinetics of dolutegravir: All factors that decrease dolutegravir exposure should be avoided in the presence of integrase class resistance.
Dolutegravir is eliminated mainly through metabolism by UGT1A1. Dolutegravir is also a substrate of UGT1A3, UGT1A9, CYP3A4, Pgp, and BCRP; therefore, medicinal products that induce those enzymes may decrease dolutegravir plasma concentration and reduce the therapeutic effect of dolutegravir (see Tables 11a, 11b and 11c). Co-administration of dolutegravir and other medicinal products that inhibit these enzymes may increase dolutegravir plasma concentration (see Tables 11a, 11b and 11c).
The absorption of dolutegravir is reduced by certain anti-acid agents (see Tables 11a, 11b and 11c).
Effect of dolutegravir on the pharmacokinetics of other agents: In vivo, dolutegravir did not have an effect on midazolam, a CYP3A4 probe. Based on in vivo and/or in vitro data, dolutegravir is not expected to affect the pharmacokinetics of medicinal products that are substrates of any major enzyme or transporter such as CYP3A4, CYP2C9 and P-gp (for more information see Pharmacology: Pharmacokinetics under Actions).
In vitro, dolutegravir inhibited the renal organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter (MATE) 1. In vivo, a 10-14% decrease of creatinine clearance (secretory fraction is dependent on OCT2 and MATE-1 transport) was observed in patients. In vivo, dolutegravir may increase plasma concentrations of medicinal products in which excretion is dependent upon OCT2 or MATE-1 (e.g. dofetilide, metformin) (see Tables 11a, 11b and 11c and Contraindications).
In vitro, dolutegravir inhibited the renal uptake transporters, organic anion transporters (OAT1) and OAT3. Based on the lack of effect on the in vivo pharmacokinetics of the OAT substrate tenofovir, in vivo inhibition of OAT1 is unlikely. Inhibition of OAT3 has not been studied in vivo. Dolutegravir may increase plasma concentrations of medical products in which excretion is dependent upon OAT3.
Emtricitabine: In vitro and clinical pharmacokinetic drug-drug interaction studies have shown that the potential for CYP-mediated interactions involving emtricitabine with other medicinal products is low. Co-administration of emtricitabine with medicinal products that are eliminated by active tubular secretion may increase concentrations of emtricitabine, and/or the co-administered medicinal product. Medicinal products that decrease renal function may increase concentrations of emtricitabine.
Tenofovir alafenamide: Tenofovir alafenamide is transported by P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Medicinal products that strongly affect P-gp activity and BCRP may lead to changes in tenofovir alafenamide absorption. Medicinal products that induce P-gp activity (e.g., rifampicin, rifabutin, carbamazepine, phenobarbital) are expected to decrease the absorption of tenofovir alafenamide, resulting in decreased plasma concentration of tenofovir alafenamide, which may lead to loss of therapeutic effect of Dolutegravir, Emtricitabine and Tenofovir alafenamide and development of resistance. Co-administration of Dolutegravir, Emtricitabine and Tenofovir alafenamide with other medicinal products that inhibit P-gp (e.g., cobicistat, ritonavir, ciclosporin) are expected to increase the absorption and plasma concentration of tenofovir alafenamide. It is not known whether the co-administration of Dolutegravir, Emtricitabine and Tenofovir alafenamide and xanthine oxidase inhibitors (e.g., febuxostat) would increase systemic exposure to tenofovir.
Tenofovir alafenamide is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6 in vitro. It is not an inhibitor of CYP3A4 in vivo. Tenofovir alafenamide is a substrate of OATP1B1 and OATP1B3 in vitro. The distribution of tenofovir alafenamide in the body may be affected by the activity of OATP1B1 and OATP1B3.
Other interactions: Interactions between potential co-administered medicinal products and the components of Dolutegravir are listed in Tables 10a, 10b and 10c and for Emtricitabine and Tenofovir alafenamide are listed in Tables 11a, 11b and 11c (increase is indicated as "↑", decrease as "↓", no change as "↔", area under the concentration versus time curve as "AUC", maximum observed concentration as "Cmax", concentration at end of dosing interval as "Cτ").
The interactions described are based on studies conducted with the components of Dolutegravir, Emtricitabine and Tenofovir alafenamide as individual agents and/or in combination, or are potential drug-drug interactions that may occur with Dolutegravir, Emtricitabine and Tenofovir alafenamide. (See Tables 10a, 10b and 10c.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

Paediatric population: Interaction studies have only been performed in adults.
Tenofovir alafenamide is not an inhibitor of human uridine diphosphate glucuronosyltransferase (UGT) 1A1 in vitro. It is not known whether tenofovir alafenamide is an inhibitor of other UGT enzymes. Emtricitabine did not inhibit the glucuronidation reaction of a non-specific UGT substrate in vitro. (See Tables 11a, 11b and 11c.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image


Click on icon to see table/diagram/image
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in