FARXIGA

Table 2:

Adverse Reactions in Placebo-Controlled Studies of Glycemic Control Reported in ≥2% of Patients Treated with FARXIGA Adverse Reaction % of Patients Pool of 12 Placebo-Controlled Studies Placebo N=1393 FARXIGA 5 mg N=1145 FARXIGA 10 mg N=1193 Female genital mycotic infections Genital mycotic infections include the following adverse reactions, listed in order of frequency reported for females: vulvovaginal mycotic infection, vaginal infection, vulvovaginal candidiasis, vulvovaginitis, genital infection, genital candidiasis, fungal genital infection, vulvitis, genitourinary tract infection, vulval abscess, and vaginitis bacterial.

(N for females: Placebo=677, FARXIGA 5 mg=581, FARXIGA 10 mg=598). 3 Urinary tract infections Urinary tract infections include the following adverse reactions, listed in order of frequency reported: urinary tract infection, cystitis, Escherichia urinary tract infection, genitourinary tract infection, pyelonephritis, trigonitis, urethritis, kidney infection, and prostatitis.

2 Increased urination Increased urination includes the following adverse reactions, listed in order of frequency reported: pollakiuria, polyuria, and urine output increased. 8 Male genital mycotic infections Genital mycotic infections include the following adverse reactions, listed in order of frequency reported for males: balanitis, fungal genital infection, balanitis candida, genital candidiasis, genital infection male, penile infection, balanoposthitis, balanoposthitis infective, genital infection, and posthitis.

(N for males: Placebo=716, FARXIGA 5 mg=564, FARXIGA 10 mg=595). 7 Pool of 13 Placebo-Controlled Studies for FARXIGA 10 mg for Glycemic Control FARXIGA 10 mg was also evaluated in a larger glycemic control placebo-controlled study pool in patients with type 2 diabetes mellitus.

This pool combined 13 placebo-controlled studies, including 3 monotherapy studies, 9 add-on to background antidiabetic therapy studies, and an initial combination with metformin study. Across these 13 studies, 2360 patients were treated once daily with FARXIGA 10 mg for a mean duration of exposure of 22 weeks.

The mean age of the population was 59 years and 4% were older than 75 years. Fifty-eight percent (58%) of the population were male; 84% were White, 9% were Asian, and 3% were Black or African American. 2%, and 30% had established microvascular disease.

73 m 2 ). Volume Depletion FARXIGA causes an osmotic diuresis, which may lead to a reduction in intravascular volume. 2) ].

Table 3:

Adverse Reactions Related to Volume Depletion Volume depletion includes reports of dehydration, hypovolemia, orthostatic hypotension, or hypotension. 1) ] is shown in Table 4. 4) ] .

Table 4:

Incidence of Severe Hypoglycemia Severe episodes of hypoglycemia were defined as episodes of severe impairment in consciousness or behavior, requiring external (third party) assistance, and with prompt recovery after intervention regardless of glucose level.

and Hypoglycemia with Glucose < 54 mg/dL Episodes of hypoglycemia with glucose <54 mg/dL (3 mmol/L) were defined as reported episodes of hypoglycemia meeting the glucose criteria that did not also qualify as a severe episode. 4) Add-on to Insulin with or without other OADs OAD = oral antidiabetic therapy.

0%) out of 8569 patients treated with placebo. Genital Mycotic Infections In the glycemic control trials, genital mycotic infections were more frequent with FARXIGA treatment. 8% on FARXIGA 10 mg, in the 12-study placebo-controlled pool.

2% of patients treated with FARXIGA 10 mg. Infections were more frequently reported in females than in males (see Table 2). The most frequently reported genital mycotic infections were vulvovaginal mycotic infections in females and balanitis in males.

0% on placebo, FARXIGA 5 mg, and FARXIGA 10 mg, respectively). 1% of patients treated with placebo. 1% of patients treated with placebo. , angioedema, urticaria, hypersensitivity) were reported with FARXIGA treatment. 3% of FARXIGA-treated patients.

If hypersensitivity reactions occur, discontinue use of FARXIGA; treat per standard of care and monitor until signs and symptoms resolve. 2) ] , events of diabetic ketoacidosis (DKA) were reported in 27 out of 8574 patients in the FARXIGA-treated group and 12 out of 8569 patients in the placebo group.

The events were evenly distributed over the study period. Laboratory Tests Increases in Serum Creatinine and Decreases in eGFR Initiation of SGLT2 inhibitors, including FARXIGA causes a small increase in serum creatinine and decrease in eGFR.

These changes in serum creatinine and eGFR generally occur within two weeks of starting therapy and then stabilize regardless of baseline kidney function. 2)] . In two studies that included patients with type 2 diabetes mellitus with moderate renal impairment, the acute effect on eGFR reversed after treatment discontinuation, suggesting acute hemodynamic changes may play a role in the renal function changes observed with FARXIGA.

Increase in Hematocrit In the pool of 13 placebo-controlled studies of glycemic control, increases from baseline in mean hematocrit values were observed in FARXIGA-treated patients starting at Week 1 and continuing up to Week 16, when the maximum mean difference from baseline was observed.

30% in the FARXIGA 10 mg group. 3% of FARXIGA 10 mg-treated patients. Increase in Low-Density Lipoprotein Cholesterol In the pool of 13 placebo-controlled studies of glycemic control, changes from baseline in mean lipid values were reported in FARXIGA-treated patients compared to placebo-treated patients.

9% for LDL cholesterol in the placebo and FARXIGA 10 mg groups, respectively. 4 mg/dL for LDL cholesterol, in FARXIGA-treated and the placebo groups, respectively. 1) ] . DAPA-HF and DELIVER Heart Failure Studies No new adverse reactions were identified in the DAPA-HF and DELIVER heart failure studies.

DAPA-CKD Chronic Kidney Disease Study No new adverse reactions were identified in the DAPA-CKD study in patients with chronic kidney disease. 2 Postmarketing Experience Additional adverse reactions have been identified during post-approval use of FARXIGA in patients with diabetes mellitus.

Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Infections:

Necrotizing fasciitis of the perineum (Fournier’s Gangrene), urosepsis and pyelonephritis Metabolism and Nutrition Disorders: Ketoacidosis Renal and Urinary Disorders: Acute kidney injury Skin and Subcutaneous Tissue Disorders: Rash

FARXIGA is not indicated for glycemic control in patients with type 1 diabetes mellitus. , history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including FARXIGA.

Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.

Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. , less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected.

2) ] ; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors. Consider ketone monitoring in patients with type 1 diabetes mellitus and consider ketone monitoring in others at risk for ketoacidosis if indicated by the clinical situation.

Assess for ketoacidosis regardless of presenting blood glucose levels in patients who present with signs and symptoms consistent with severe metabolic acidosis. Monitor patients for resolution of ketoacidosis before restarting FARXIGA.

Withhold FARXIGA, if possible, in temporary clinical situations that could predispose patients to ketoacidosis. 3) ] . Educate all patients on the signs and symptoms of ketoacidosis and instruct patients to discontinue FARXIGA and seek medical attention immediately if signs and symptoms occur.

2 Volume Depletion FARXIGA can cause intravascular volume depletion which may sometimes manifest as symptomatic hypotension or acute transient changes in creatinine. There have been post-marketing reports of acute kidney injury, some requiring hospitalization and dialysis, in patients with type 2 diabetes mellitus receiving SGLT2 inhibitors, including FARXIGA.

73 m 2 ), elderly patients, or patients on loop diuretics may be at increased risk for volume depletion or hypotension. Before initiating FARXIGA in patients with one or more of these characteristics, assess volume status and renal function.

Monitor for signs and symptoms of hypotension, and renal function after initiating therapy. 3 Urosepsis and Pyelonephritis Serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization have been reported in patients receiving SGLT2 inhibitors, including FARXIGA.

Treatment with SGLT2 inhibitors increases the risk for urinary tract infections. Evaluate patients for signs and symptoms of urinary tract infections and treat promptly, if indicated [see Adverse Reactions (6) ] . 4 Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues Insulin and insulin secretagogues are known to cause hypoglycemia.

1) ] . Therefore, a lower dose of insulin or insulin secretagogue may be required to minimize the risk of hypoglycemia when these agents are used in combination with FARXIGA. 5 Necrotizing Fasciitis of the Perineum (Fournier’s Gangrene) Reports of necrotizing fasciitis of the perineum (Fournier’s Gangrene), a rare but serious and life-threatening necrotizing infection requiring urgent surgical intervention, have been identified in postmarketing surveillance in patients with diabetes mellitus receiving SGLT2 inhibitors, including FARXIGA.

Cases have been reported in both females and males. Serious outcomes have included hospitalization, multiple surgeries, and death. Patients treated with FARXIGA presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise, should be assessed for necrotizing fasciitis.

If suspected, start treatment immediately with broad-spectrum antibiotics and, if necessary, surgical debridement. Discontinue FARXIGA, closely monitor blood glucose levels, and provide appropriate alternative therapy for glycemic control.

6 Genital Mycotic Infections FARXIGA increases the risk of genital mycotic infections. 1) ] . Monitor and treat appropriately.