Lack of Pharmacokinetic Interactions Between Dapagliflozin and Simvastatin, Valsartan, Warfarin, or Digoxin

Kasichayanula, Sreeneeranj; Chang, Ming; Liu, Xiaoni; Shyu, Wen-Chyi; Griffen, Steven C.; LaCreta, Frank; Boulton, David W.

doi:10.1007/s12325-011-0098-x

Cited by 51 publications

(49 citation statements)

References 30 publications

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“…The coadministration with simvastatin did not induce any clinically meaningful effect on the pharmacokinetics of dapagliflozin, but increased the area under the curve for simvastatin by 19% and simvastatin acid by 30% [Kasichayanula et al 2012]. These increases do not seem clinically meaningful, but caution should be taken when dapagliflozin and simvastatin are coadministered.…”

Section: Drug Interactionsmentioning

confidence: 86%

Dapagliflozin in patients with type 2 diabetes mellitus

Filippatos

Liberopoulos

Elisaf

2014

Therapeutic Advances in Endocrinology

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Mechanism of action SGLT2 mediates approximately 90% of active renal glucose reabsorption in the S1 segment of early proximal tubule of the kidney [Vallon et al. 2011]. Dapagliflozin is a selective and reversible inhibitor of SGLT2, leading to a significant reduction in glucose reabsorption and decrease of serum glucose concentration in an insulin-independent manner [Balakumar et al. 2014]. Dapagliflozin also improves insulin sensitivity but enhances endogenous glucose production in patients with T2DM [Merovci et al. 2014; Mudaliar et al. 2014]. The reduction in glucose reabsorption by dapagliflozin has been associated

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Section: Drug Interactionsmentioning

confidence: 86%

Dapagliflozin in patients with type 2 diabetes mellitus

Filippatos

Liberopoulos

Elisaf

2014

Therapeutic Advances in Endocrinology

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“…Simvastatin and valsartan did not influence the exposure to dapagliflozin ( A mild increase in the exposure to R-warfarin and S-warfarin was also detected when warfarin was prescribed with dapagliflozin (Table 2), without any change in the International Normalized Ratio (INR : GMR : 1.007; 90% CI : 0.989-1.025) [38] . No other meaningful DDIs were detected, including changes in digoxin levels after dapagliflozin administration [38] (Table 2). …”

Section: Dapagliflozinmentioning

confidence: 97%

“…Co-administration of dapagliflozin was evaluated with simvastatin, valsartan, warfarin, or digoxin in healthy volunteers [38] . Simvastatin and valsartan did not influence the exposure to dapagliflozin ( A mild increase in the exposure to R-warfarin and S-warfarin was also detected when warfarin was prescribed with dapagliflozin (Table 2), without any change in the International Normalized Ratio (INR : GMR : 1.007; 90% CI : 0.989-1.025) [38] .…”

Section: Dapagliflozinmentioning

confidence: 99%

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Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

Scheen

2014

Clin Pharmacokinet

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SUMMARYInhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin, without inducing hypoglycaemia, as monotherapy or in combination with various other glucose-lowering agents, with the add-on value of promoting some weight loss and lowering arterial blood pressure. As they may be used concomitantly with many other drugs, we review the potential drug-drug interactions regarding the three leaders in the class (dapagliglozin, canagliflozin and empagliflozin). Most of the available studies were performed in healthy volunteers and have assessed the pharmacokinetic interferences with a single administration of the SGLT2 inhibitor. The exposure (assessed by peak plasma concentrations -C max -and area under the concentrationtime curve -AUC -) to each SGLT2 inhibitor tested was not significantly influenced by the concomitant administration of other glucose lowering agents or cardiovascular agents commonly used in patients with type 2 diabetes. Reciprocally, these medications did not influence the pharmacokinetic parameters of dapagliflozin, canagliflozin or empagliflozin.Some modest changes were not considered as clinically relevant. However, drugs which could specifically interfere with the metabolic pathways of SGLT2 inhibitors (rifampin, inhibitors or inducers of uridine diphosphate-glucuronosyltransferase -UGT -) may result in significant changes in the exposure of SGLT2 inhibitors, as shown for dapagliflozin and canagliflozin.Potential drug-drug interactions in patients with type 2 diabetes receiving a chronic treatment with a SGLT2 inhibitor deserve further attention, especially in the numerous individuals treated with several medications or in more fragile patients with hepatic and/or renal impairment.

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“…1,7 No pharmacokinetic interactions were observed with coadministration of dapaglifl ozin and metformin, glimepiride, pioglitazone, sitagliptin, hydrochlorothiazide, bumetanide, simvastatin, valsartan, warfarin, or digoxin. 1,[37][38][39][40] Patients receiving loop diuretics may be at increased risk for symptomatic hypotension upon initiation of dapaglifl ozin therapy. 1 Coadministration of rifampin, a UGT1A9 inducer, reduced dapaglifl ozin exposure, whereas concomitant administration of mefenamic acid, a UGT1A9 inhibitor, increased dapaglifl ozin exposure; however, neither change was considered clinically signifi cant.…”

Section: Drug Interactionsmentioning

confidence: 99%

Dapagliflozin

Cada¹,

Levien

Baker

2014

Hosp Pharm

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Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800–322–4349. The July 2014 monograph topics are albiglutide, ramucirumab, short ragweed pollen allergen extract, timothy grass pollen allergen extract, and isavuconazole. The DUE/MUE is on albiglutide.

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Lack of Pharmacokinetic Interactions Between Dapagliflozin and Simvastatin, Valsartan, Warfarin, or Digoxin

Abstract: Introduction: Coronary heart disease, stroke,

Cited by 51 publications

References 30 publications

Dapagliflozin in patients with type 2 diabetes mellitus

Dapagliflozin in patients with type 2 diabetes mellitus

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

Dapagliflozin

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