Glyxambi Drug Interactions

No interactions between the two components of this fixed-dose combination have been observed in clinical studies.
No drug interaction studies have been performed with GLYXAMBI and other medicinal products, however, such studies have been conducted with the individual active substances.
No clinically meaningful pharmacokinetic interactions were observed when empagliflozin or linagliptin were co-administered with other commonly used medicinal products. Based on results of pharmacokinetic studies, no dose adjustment of GLYXAMBI is recommended when co-administered with commonly prescribed medicinal products (see Pharmacology under Actions), except those mentioned as follows.
Insulin and sulphonylureas: Insulin and sulphonylureas may increase the risk of hypoglycaemia. Therefore, a lower dose of insulin or sulphonylureas may be required to reduce the risk of hypoglycaemia when used in combination with GLYXAMBI (see Dosage & Administration, Precautions, Side Effects).
Diuretics: Empagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension (see Precautions).
Interference with 1,5-anhydroglucitol (1,5-AG) Assay: Monitoring glycemic control with 1,5-AG assay is not recommended as measurements of 1,5-AG are unreliable in assessing glycemic control in patients taking SGLT2 inhibitors. Use alternative methods to monitor glycemic control.
UGT inhibitors and inducers: Empagliflozin is primarily metabolised via uridine 5'-diphosphoglucuronosyltransferases (UGT); however, a clinically relevant effect of UGT inhibitors on empagliflozin is not expected (see Pharmacology under Actions).
The effect of UGT induction on empagliflozin has not been studied. Co-medication with known inducers of UGT enzymes should be avoided because of a risk of decreased efficacy of empagliflozin.
Inducers of P-gp or CYP3A4 isozymes: Co-administration of rifampicin decreased linagliptin exposure by 40%, suggesting that the efficacy of linagliptin may be reduced when administered in combination with a strong P-glycoprotein (P-gp) or cytochrome P450 (CYP) isozyme CYP3A4 inducer, particularly if these are administed long-term (see Pharmacology under Actions). Co-administration with other potent inducers of P-gp and CYP3A4, such as carbamazepine, phenobarbital and phenytoin, has not been studied.
Inhibitors of P-gp or CYP3A4 isozymes: Co-administration of a single 5mg oral dose of linagliptin and multiple 200mg oral doses of ritonavir, a potent inhibitor of P-glycoprotein and CYP3A4, increased the AUC and Cmax of linagliptin approximately two fold and three fold, respectively. The unbound concentrations, which are usually less than 1% at the therapeutic dose of linagliptin, were increased 4 to 5-fold after co-administration with ritonavir. Simulations of steady-state plasma concentrations of linagliptin with and without ritonavir indicated that the increase in exposure will be not associated with an increased accumulation. These changes in linagliptin pharmacokinetics were not considered to be clinically relevant. Therefore, clinically relevant interactions would not be expected with other P-glycoprotein / CYP3A4 inhibitors.