Physicians Office Resource Volume 11 Issue 01 | Page 3

JARDIANCE ® ( empagliflozin ) tablets , for oral use BRIEF SUMMARY OF PRESCRIBING INFORMATION Please see package insert for full Prescribing Information .

INDICATIONS AND USAGE : JARDIANCE is indicated : as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ; to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease . Limitations of Use : JARDIANCE is not recommended for patients with type 1 diabetes or for the treatment of diabetic ketoacidosis .

CONTRAINDICATIONS : History of serious hypersensitivity reaction to JARDIANCE ; Severe renal impairment , end-stage renal disease , or dialysis [ see Use in Specific Populations ].

WARNINGS AND PRECAUTIONS : Hypotension : JARDIANCE causes intravascular volume contraction . Symptomatic hypotension may occur after initiating JARDIANCE [ see Adverse Reactions ] particularly in patients with renal impairment , the elderly , in patients with low systolic blood pressure , and in patients on diuretics . Before initiating JARDIANCE , assess for volume contraction and correct volume status if indicated . Monitor for signs and symptoms of hypotension after initiating therapy and increase monitoring in clinical situations where volume contraction is expected [ see Use in Specific Populations ]. Ketoacidosis : Reports of ketoacidosis , a serious life-threatening condition requiring urgent hospitalization have been identified in postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 ( SGLT2 ) inhibitors , including JARDIANCE . Fatal cases of ketoacidosis have been reported in patients taking JARDIANCE . JARDIANCE is not indicated for the treatment of patients with type 1 diabetes mellitus [ see Indications and Usage ]. Patients treated with JARDIANCE who present with signs and symptoms consistent with severe metabolic acidosis should be assessed for ketoacidosis regardless of presenting blood glucose levels , as ketoacidosis associated with JARDIANCE may be present even if blood glucose levels are less than 250 mg / dL . If ketoacidosis is suspected , JARDIANCE should be discontinued , patient should be evaluated , and prompt treatment should be instituted . Treatment of ketoacidosis may require insulin , fluid and carbohydrate replacement . In many of the postmarketing reports , and particularly in patients with type 1 diabetes , the presence of ketoacidosis was not immediately recognized and institution of treatment was delayed because presenting blood glucose levels were below those typically expected for diabetic ketoacidosis ( often less than 250 mg / dL ). Signs and symptoms at presentation were consistent

with dehydration and severe metabolic acidosis and included nausea , vomiting , abdominal pain , generalized malaise , and shortness of breath . In some but not all cases , factors predisposing to ketoacidosis such as insulin dose reduction , acute febrile illness , reduced caloric intake due to illness or surgery , pancreatic disorders suggesting insulin deficiency ( e . g ., type 1 diabetes , history of pancreatitis or pancreatic surgery ), and alcohol abuse were identified . Before initiating JARDIANCE , consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause , caloric restriction , and alcohol abuse . In patients treated with JARDIANCE consider monitoring for ketoacidosis and temporarily discontinuing JARDIANCE in clinical situations known to predispose to ketoacidosis ( e . g ., prolonged fasting due to acute illness or surgery ). Acute Kidney Injury

and Impairment in Renal Function : JARDIANCE causes intravascular volume contraction [ see Warnings and Precautions ] and can cause renal impairment [ see Adverse Reactions ]. There have been postmarketing reports of acute kidney injury , some requiring hospitalization and dialysis , in patients receiving SGLT2 inhibitors , including JARDIANCE ; some reports involved patients younger than 65 years of age . Before initiating JARDIANCE , consider factors that may predispose patients to acute kidney injury including hypovolemia , chronic renal insufficiency , congestive heart failure and concomitant medications ( diuretics , ACE inhibitors , ARBs , NSAIDs ). Consider temporarily discontinuing JARDIANCE in any setting of reduced oral intake ( such as acute illness or fasting ) or fluid losses ( such as gastrointestinal illness or excessive heat exposure ); monitor patients for signs and symptoms of acute kidney injury . If

acute kidney injury occurs , discontinue JARDIANCE promptly and institute treatment . JARDIANCE increases serum creatinine and decreases eGFR . Patients with hypovolemia may be more susceptible to these changes . Renal function abnormalities can occur after initiating JARDIANCE [ see Adverse Reactions ]. Renal function should be evaluated prior to initiation of JARDIANCE and monitored periodically thereafter . More frequent renal function monitoring is recommended in patients with an eGFR below 60 mL / min / 1.73 m 2 . Use of JARDIANCE is not recommended when eGFR is persistently less than 45 mL / min / 1.73 m 2 and is contraindicated in patients with an eGFR less than 30 mL / min / 1.73 m 2 [ see Contraindications , Use in Specific Populations ].

Urosepsis and Pyelonephritis : There have been postmarketing reports of serious urinary tract infections including urosepsis and pyelonephritis requiring hospitalization in patients receiving SGLT2 inhibitors , including JARDIANCE . 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 ]. Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues : Insulin and insulin secretagogues are known to cause hypoglycemia . The risk of hypoglycemia is increased when JARDIANCE is used in combination with insulin secretagogues ( e . g ., sulfonylurea ) or insulin [ see Adverse Reactions ]. Therefore , a lower dose of the insulin secretagogue or insulin may be required to reduce the risk of hypoglycemia when used in combination with JARDIANCE . Genital Mycotic Infections : JARDIANCE increases the risk for genital mycotic infections [ see Adverse Reactions ]. Patients with a history of chronic or recurrent genital mycotic infections were more likely to develop mycotic genital infections . Monitor and treat as appropriate . Increased Low-Density Lipoprotein Cholesterol ( LDL-C ): Increases in LDL-C can occur with JARDIANCE [ see Adverse Reactions ]. Monitor and treat as appropriate .

ADVERSE REACTIONS : The following important adverse reactions are described below and elsewhere in the labeling : Hypotension [ see Warnings and Precautions ]; Ketoacidosis [ see Warnings and Precautions ]; Acute Kidney Injury and Impairment in Renal Function [ see Warnings and Precautions ]; Urosepsis and Pyelonephritis [ see Warnings and Precautions ]; Hypoglycemia with Concomitant Use with Insulin and Insulin Secretagogues [ see Warnings and Precautions ]; Genital Mycotic Infections [ see Warnings and Precautions ]; Increased Low-Density Lipoprotein Cholesterol ( LDL-C ) [ see Warnings and Precautions ]. Clinical Trials Experience : Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice . Pool of Placebo-Controlled Trials evaluating JARDIANCE 10 and 25 mg : The data in Table 1 are derived from a pool of four 24-week placebocontrolled trials and 18-week data from a placebo-controlled trial with insulin . JARDIANCE was used as monotherapy in one trial and as add-on therapy in four trials . These data reflect exposure of 1976 patients to JARDIANCE with a mean exposure duration of approximately 23 weeks . Patients received placebo ( N = 995 ), JARDIANCE 10 mg ( N = 999 ), or JARDIANCE 25 mg ( N = 977 ) once daily . The mean age of the population was 56 years and 3 % were older than 75 years of age . More than half ( 55 %) of the population was male ; 46 % were White , 50 % were Asian , and 3 % were Black or African American . At baseline , 57 % of the population had diabetes more than 5 years and had a mean hemoglobin A1c ( HbA1c ) of 8 %. Established microvascular complications of diabetes at baseline included diabetic nephropathy ( 7 %), retinopathy ( 8 %), or neuropathy ( 16 %). Baseline renal function was normal or mildly impaired in 91 % of patients and moderately impaired in 9 % of patients ( mean eGFR 86.8 mL / min / 1.73 m 2 ). Table 1 shows common adverse reactions ( excluding hypoglycemia ) associated with the use of JARDIANCE . The adverse reactions were not present at baseline , occurred more commonly on JARDIANCE than on placebo and occurred in greater than or equal to 2 % of patients treated with JARDIANCE 10 mg or JARDIANCE 25 mg .

Table 1 : Adverse Reactions Reported in ≥2 % of Patients Treated with JARDIANCE and Greater than Placebo in Pooled Placebo-Controlled Clinical Studies of JARDIANCE Monotherapy or Combination Therapy

Placebo N = 995

Number (%) of Patients JARDIANCE 10 mg JARDIANCE 25 mg

N = 999 N = 977

Thirst ( including polydipsia ) was reported in 0 %, 1.7 %, and 1.5 % for placebo , JARDIANCE 10 mg , and JARDIANCE 25 mg , respectively . Volume Depletion : JARDIANCE causes an osmotic diuresis , which may lead to intravascular volume contraction and adverse reactions related to volume depletion . In the pool of five placebo-controlled clinical trials , adverse reactions related to volume depletion ( e . g ., blood pressure ( ambulatory ) decreased , blood pressure systolic decreased , dehydration , hypotension , hypovolemia , orthostatic hypotension , and syncope ) were reported by 0.3 %, 0.5 %, and 0.3 % of patients treated with placebo , JARDIANCE 10 mg , and JARDIANCE 25 mg respectively . JARDIANCE may increase the risk of hypotension in patients at risk for volume contraction [ see Warnings and Precautions and Use in Specific Populations ]. Increased Urination : In the pool of five placebo-controlled clinical trials , adverse reactions of increased urination ( e . g ., polyuria , pollakiuria , and nocturia ) occurred more frequently on JARDIANCE than on placebo ( see Table 1 ). Specifically , nocturia was reported by 0.4 %, 0.3 %, and 0.8 % of patients treated with placebo , JARDIANCE 10 mg , and JARDIANCE 25 mg , respectively . Acute Impairment in Renal Function : Treatment with JARDIANCE was associated with increases in serum creatinine and decreases in eGFR ( see Table 2 ). Patients with moderate renal impairment at baseline had larger mean changes . [ see Warnings and Precautions and Use in Specific Populations ]. In a long-term cardiovascular outcome trial , the acute impairment in renal function was observed to reverse after treatment discontinuation suggesting acute hemodynamic changes play a role in the renal function changes observed with empagliflozin .

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