SYNJARDYXR(empagliflozin and metformin hydrochloride extended-release) tablets(二十四)
rmin hydrochloride
Table 5 Effect of Coadministered Drug on Plasma Metformin Systemic Exposure
* All metformin and coadministered drugs were given as single doses
† AUC = AUC(INF)
≠ Metformin hydrochloride extended-release tablets 500 mg
‡ Ratio of arithmetic means
**At steady state with topiramate 100 mg every 12 hours and metformin 500 mg every 12 hours; AUC = AUC0-12h
Coadministered
Drug Dosing of Coadministered
Drug* Dose of Metformin
hydrochloride* Geometric Mean Ratio
(ratio with/without coadministered drug)
No effect=1.0
AUC† Cmax
No dosing adjustments required for the following coadministered drugs:
Glyburide 5 mg 500 mg≠ metformin 0.98‡ 0.99‡
Furosemide 40 mg 850 mg metformin 1.09‡ 1.22‡
Nifedipine 10 mg 850 mg metformin 1.16 1.21
Propranolol 40 mg 850 mg metformin 0.90 0.94
Ibuprofen 400 mg 850 mg metformin 1.05‡ 1.07‡
Drugs that are eliminated by renal tubular secretion may increase the accumulation of metformin [see WARNINGS AND PRECAUTIONS (5.1) and DRUG INTERACTIONS (7.1)].
Cimetidine 400 mg 850 mg metformin 1.40 1.61
Carbonic anhydrase inhibitors may cause metabolic acidosis [see WARNINGS AND PRECAUTIONS (5.1) and DRUG INTERACTIONS (7.1)].
Topiramate** 100 mg 500 mg metformin 1.25 1.17
Table 6 Effect of Metformin on Coadministered Drug Systemic Exposure
* All metformin and coadministered drugs were given as single doses
† AUC = AUC(INF) unless otherwise noted
§ AUC(0-24 hr) reported
‡ Ratio of arithmetic means, p-value of difference <0.05
¶ Ratio of arithmetic means
Coadministered
Drug Dosing of Coadministered
Drug* Dose of Metformin
hydrochloride* Geometric Mean Ratio
(ratio with/without metformin)
No effect=1.0
AUC† Cmax
No dosing adjustments required for the following coadministered drugs:
Glyburide 5 mg 500 mg§ glyburide 0.78‡ 0.63‡
Furosemide 40 mg 850 mg furosemide 0.87‡ 0.69‡
Nifedipine 10 mg 850 mg nifedipine 1.10§ 1.08
Propranolol 40 mg 850 mg propranolol 1.01§ 0.94
Ibuprofen 400 mg 850 mg ibuprofen 0.97¶ 1.01¶
Cimetidine 400 mg 850 mg cimetidine 0.95§ 1.01 CLOSE
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
SYNJARDY XR
No animal studies have been conducted with the combination of empagliflozin and metformin hydrochloride to eva luate carcinogenesis, mutagenesis, or impairment of fertility. General toxicity studies in rats up to 13 weeks were performed with the combined components. These studies indicated that no additive toxicity is caused by the combination of empagliflozin and metformin.
Empagliflozin
Carcinogenesis
Carcinogenesis was eva luated in 2-year studies conducted in CD-1 mice and Wistar rats. Empagliflozi |
