Body Mass Index (BMI)/Weight
No dose adjustment is necessary based on BMI/weight. BMI/weight had no clinically meaningful effect on the pharmacokinetics of linagliptin based on a population pharmacokinetic analysis.

Gender
No dose adjustment is necessary based on gender. Gender had no clinically meaningful effect on the pharmacokinetics of linagliptin based on a population pharmacokinetic analysis.

Geriatric
No dose adjustment is recommended based on age, as age did not have a clinically meaningful impact on the pharmacokinetics of linagliptin based on a population pharmacokinetic analysis.

Pediatric
Studies characterizing the pharmacokinetics of linagliptin in pediatric patients have not yet been performed.

Race
No dose adjustment is necessary based on race. Race had no clinically meaningful effect on the pharmacokinetics of linagliptin based on available pharmacokinetic data, including subjects of White, Hispanic, Black, and Asian racial groups.

Drug Interactions

In vitro Assessment of Drug Interactions
Linagliptin is a weak to moderate inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes and is not an inducer of CYP isozymes, including CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 4A11.

Linagliptin is a P-glycoprotein (P-gp) substrate, and inhibits P-gp mediated transport of digoxin at high concentrations. Based on these results and in vivo drug interaction studies, linagliptin is considered unlikely to cause interactions with other P-gp substrates at therapeutic concentrations.

In vivo Assessment of Drug Interactions
Inducers of CYP3A4 or P-gp (e.g., rifampin) decrease exposure to linagliptin to subtherapeutic and likely ineffective concentrations. For patients requiring use of such drugs, an alternative to linagliptin is strongly recommended. In vivo studies indicated evidence of a low propensity for causing drug interactions with substrates of CYP3A4, CYP2C9, CYP2C8, P-gp and organic cationic transporter (OCT). No dose adjustment of TRADJENTA is recommended based on results of the described pharmacokinetic studies.

Table 2 Effect of Coadministered Drugs on Systemic Exposure of Linagliptin Coadministered Drug Dosing of Coadministered Drug* Dosing of Linagliptin* Geometric Mean Ratio
(ratio with/without coadministered drug)
No effect = 1.0
AUC† Cmax
*Multiple dose (steady state) unless otherwise noted
# Single dose
†AUC = AUC(0 to 24 hours) for single dose treatments and AUC = AUC(TAU) for multiple dose treatments
QD = once daily
BID = twice daily
TID = three times daily
Metformin  850 mg TID 10 mg QD 1.20 1.03
Glyburide  1.75 mg# 5 mg QD 1.02 1.01
Pioglitazone 45 mg QD 10 mg QD 1.13 1.07
Ritonavir 200 mg BID 5 mg# 2.01 2.96
Rifampin  600 mg QD 5 mg QD 0.60  0.56
Table 3 Effect of Linagliptin on Systemic Exposure of Coadministered Drugs Coadministered Drug Dosing of Coadministered Drug* Dosing of Linagliptin* Geometric Mean Ratio
(ratio with/without coadministered drug)
No effect = 1.0 
  AUC† Cmax
* Multiple dose (steady state) unless otherwise noted
# Single dos