Farxiga (Dapagliflozin) Complete Drug-Drug Interaction Profile

The four interactions the Farxiga label flags

The drug interactions section of the current Farxiga label (effective June 2026) lists four clinically relevant interactions, then adds study tables showing which coadministered drugs changed dapagliflozin exposure and which drugs dapagliflozin changed [1].

Insulin and insulin secretagogues

Insulin and insulin secretagogues such as sulfonylureas both cause hypoglycemia, and the label says Farxiga may increase that risk when they are combined. The label's instruction is that a lower dose of the insulin or the insulin secretagogue may be required to reduce hypoglycemia risk [1]. This is a pharmacodynamic interaction: the label's pharmacokinetic tables show glimepiride did not change dapagliflozin exposure, and dapagliflozin raised glimepiride AUC by 13% [1].

Lithium

The direction here is easy to get backwards. The label says concomitant use of an SGLT2 inhibitor with lithium may decrease serum lithium concentrations, and advises monitoring serum lithium more frequently during Farxiga initiation and dosage changes [1]. It is a falling level, not lithium toxicity from rising levels, that the label describes. Lithium is not one of the drugs in the label's exposure tables, so the statement rests on the interaction table rather than on a measured change in lithium levels [1].

Diuretics and volume depletion

Dapagliflozin causes an osmotic diuresis, and volume depletion is a Warnings and Precautions item. The label says patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2), older patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension, and that volume status and renal function should be assessed before starting and monitored afterward [1].

The label tells clinicians to correct volume depletion before initiating Farxiga [1]. Among DECLARE-TIMI 58 participants taking loop diuretics, volume-depletion events occurred in 6.6% of those on dapagliflozin and 6.1% of those on placebo [1]. Across the 12 pooled glycemic-control trials, volume depletion events were 0.4% on placebo, 0.6% on 5 mg and 0.8% on 10 mg; in DECLARE it was 2.4% on placebo versus 2.5% on 10 mg [1].

Urine glucose tests and the 1,5-AG assay

Because the drug works by spilling glucose into urine, urine glucose tests turn positive. The Farxiga label recommends other methods for monitoring blood sugar because urine glucose tests will be positive during treatment [1]. Measurements of 1,5-anhydroglucitol are also unreliable in these patients, and the label likewise says not to use that assay for monitoring [1].

Pharmacokinetic interactions: what the label's studies showed

Rifampin

Rifampin 600 mg once daily for 6 days lowered dapagliflozin AUC by 22% (90% CI 17% to 27% lower) and peak concentration by 7%, with no dose adjustment recommended for dapagliflozin [1].

Mefenamic acid

Mefenamic acid (500 mg loading dose, then 250 mg every 6 hours for 14 doses) raised dapagliflozin AUC by 51% (90% CI 44% to 58%) and peak concentration by 13% (90% CI 3% to 24%), again with no dose adjustment recommended [1].

Drugs that did not change dapagliflozin exposure

No change in dapagliflozin exposure was seen with metformin 1000 mg, pioglitazone 45 mg, sitagliptin 100 mg, glimepiride 4 mg, voglibose 0.2 mg three times daily, hydrochlorothiazide 25 mg, bumetanide 1 mg, or simvastatin 40 mg. Valsartan 320 mg lowered dapagliflozin peak concentration by 12% (90% CI 3% to 20% lower) with AUC unchanged [1].

What dapagliflozin did to other drugs

Dapagliflozin did not meaningfully change exposure to metformin, sitagliptin, hydrochlorothiazide, digoxin 0.25 mg or warfarin 25 mg. Glimepiride AUC rose 13%, bumetanide peak and AUC each rose 13%, and simvastatin AUC rose 19% with peak concentration unchanged. Pioglitazone peak fell 7% with AUC unchanged, and valsartan peak fell 6% with AUC up 5%. The label recommends no dosing adjustments for any of these [1].

Does dapagliflozin interact with statins, warfarin or digoxin?

In the label's studies, simvastatin AUC was 19% higher with dapagliflozin, while digoxin and warfarin exposures were unchanged. The label recommends no dosing adjustment for simvastatin, warfarin or digoxin [1].

Why the CYP interaction list is short

In in vitro studies, dapagliflozin and its 3-O-glucuronide neither inhibited CYP1A2, 2C9, 2C19, 2D6 or 3A4 nor induced CYP1A2, 2B6 or 3A4 [1]. Dapagliflozin is a weak P-glycoprotein substrate and the glucuronide is an OAT3 substrate; neither meaningfully inhibited P-gp, OCT2, OAT1 or OAT3, and the label concludes dapagliflozin is unlikely to affect drugs that are substrates of those transporters [1].

Dapagliflozin is metabolized mainly by UGT1A9 to an inactive glucuronide, with CYP playing a minor role; it is about 91% protein bound, has a half-life of about 12.9 hours, and is eliminated as 75% urine and 21% feces, with under 2% of the urine fraction being unchanged drug [1].

These interaction findings come from the Farxiga tablet label. Generic dapagliflozin tablets from multiple manufacturers carry FDA labels, and the fixed-dose combinations with metformin (Xigduo XR) and with saxagliptin are separate products with their own labels and their own warnings [1][2].

Other safety points that depend on what else a patient is taking

The label's Warnings and Precautions section ties several safety issues to other medicines or circumstances. Hypoglycemia is the insulin and secretagogue issue above [1]. For volume depletion, the label separately reports postmarketing acute kidney injury with SGLT2 inhibitors, including cases requiring hospitalization and dialysis, and lists loop diuretics among the risk factors for volume depletion or hypotension. The label also advises withholding Farxiga for at least 3 days, if possible, before surgery or procedures with prolonged fasting [1].

Ketoacidosis is listed as a separate warning. The label says to assess for it regardless of presenting blood glucose, noting that levels at presentation may be below 250 mg/dL, and it names under-insulinization from reduced or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion and alcohol abuse as precipitating conditions [1]. The label's contraindication is limited to a history of serious hypersensitivity to dapagliflozin or an excipient; anaphylaxis and angioedema have been reported [1].