ythmia, asystole, second degree atrioventricular block, hypotension, elevation in blood pressure, bradycardia, and tachycardia have been reported generally within 60 minutes following administration of indigotindisulfonate sodium injection products and required urgent intervention [see adverse reactions ( 6.2 )]. indigotindisulfonate may cause vasoconstriction by interference with vasodilation mediated by nitric oxide dependent mechanisms and by direct vasoconstriction. indigotindisulfonate may also cause hypotension. patients with hypertension, heart rate and conduction disorders, or medications causing bradycardia may be at increased risk for elevated blood pressure, hypotension, and bradycardia. closely monitor blood pressure and cardiac rhythm during and following the injection of bludigo. interrupt administration if reactions are observed. 5.2 hypersensitivity reactions serious anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, or erythema have been reported with the use of indigotindisulfonate sodium injection products [see adverse reactions ( 6.2 )] . bludigo is contraindicated in patients with known hypersensitivity to indigotindisulfonate [see contraindications ( 4 )] . monitor patients for anaphylactic reactions and have emergency equipment and trained personnel readily available. 5.3 interference with oximetry measurements indigotindisulfonate has been reported to interfere with light absorption and transiently interfere with pulse oximetric methods. anesthesiologists should be aware of the potential for artifactual reduction in spo 2 when anesthetized patients are administered bludigo.

were treated intravenously; 58 (49%) of these patients received one dose of bludigo 2.5 ml and 60 (51%) of patients received one dose of bludigo 5 ml. the 2.5 ml dose is not approved [see dosage and administration ( 2.1 )] . the mean age of patients was 51 years and 35 (30%) patients were 65 years of age or older. the majority of patients were white 105 (89%) and female 87 (74%). the adverse reactions (≥1%) reported in the clinical trial are provided in table 1. table 1. adverse reactions reported at ≥1% of patients receiving bludigo 5 ml intravenously bludigo 5 ml (n=60) n (%) constipation 3 (5.0) nausea 2 (3.3) vomiting 2 (3.3) abdominal pain 2 (3.3) pyrexia 2 (3.3) alt increase 2 (3.3) dysuria 1 (1.7) 6.2 postmarketing experience the following adverse reactions have been identified following the use of indigotindisulfonate sodium injection products. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. cardiovascular disorders: cardiac arrest, arrhythmia, asystole, atrioventricular block second degree, hypotension, elevation in blood pressure, bradycardia, tachycardia general disorders and administration site conditions: injection site discoloration immune system disorders: anaphylactic reactions with hypotension, dyspnea, bronchospasm, urticaria, erythema

digotindisulfonate sodium during pregnancy cannot be evaluated from the data available . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defects, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 8.2 lactation risk summary it is not known if indigotindisulfonate is present in animal or human milk. the transfer of indigotindisulfonate into breastmilk is likely to be low and adverse effects on the breastfed infant are not expected [see clinical pharmacology ( 12.3 )] . there are no data on the effect of indigotindisulfonate on the breastfed infant or milk production. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for bludigo and any potential adverse effects on the breastfed infant from bludigo or from the underlying maternal condition. 8.4 pediatric use the safety and effectiveness of bludigo have not been established in pediatric patients. 8.5 geriatric use of the total number of subjects in the clinical study of bludigo, 23 (20%) were 65 to 74 years of age, and 12 (10%) were 75 and older. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 renal impairment indigotindisulfonate is known to be excreted by the kidney through tubular secretion. no dedicated pharmacokinetic study using bludigo in patients with varying degree of renal impairment has been conducted. based on subgroup analyses in the randomized clinical trial, dose adjustment is not needed in patients with mild to moderate renal impairment (estimated glomerular filtration rate (egfr) 30 to 89 ml/min derived from the modification of diet in renal disease formula). bludigo has not been studied in patients with egfr < 30 ml/min and is not recommended for use in these patients.

jor birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defects, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

44.0) feces <2% a unchanged drug c max = maximum plasma concentration; auc 0-inf =area under the plasma concentration-time curve from time of administration extrapolated to infinity; cv=coefficient of variation

es with indigotindisulfonate sodium using the intravenous route of administration have not been conducted.

te sodium using the intravenous route of administration have not been conducted.

n, with separate recordings made following sodium chloride injection and bludigo. the conspicuity of the urine flow from the ureteral orifices was assessed in a randomized, blinded fashion by two independent central reviewers using a 5-point scale (1 = no urine flow observed; 2 = weak urine flow, little color contrast; 3 = color contrast or significant urine flow; 4 = strong urine flow with good color contrast; and 5 = strong urine flow with striking contrast in color) once after sodium chloride injection and twice after bludigo resulting in paired data. the surgeons also reviewed and scored conspicuity of the urine flow from the ureteral orifices. the responder for a ureter is defined as the difference in conspicuity score between bludigo and sodium chloride injection being at least one point difference and the conspicuity score following bludigo alone being greater than or equal to three. the reviewer agreement with the responder endpoint is acceptable. the proportion of responders along with its 95% confidence interval by ureter and reviewer or surgeon is summarized in table 3. table 3. summary of proportion of responders by ureter and reviewer or surgeon in patients receiving bludigo 5 ml bludigo 5 ml left ureter (n=49) right ureter (n=49) reviewer 1 % responder* 95% cl** 63% (48%, 77%) 76% (61%, 87%) reviewer 2 % responder 95% cl 78% (63%, 88%) 82% (68%, 91%) surgeon % responder 95% cl 71% (57%, 83%) 82% (68%, 91%) *responder: ic conspicuity score ≥ 3 and difference (ic – saline) in conspicuity score ≥1, missing data is imputed as non-responder ** two-sided 95% confidence limits for the proportion of responder, calculated using the clopper-pearson (exact) method